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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-02486 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| NRG-LU003 | Other Identifier | NRG Oncology | |
| NRG-LU003 | Other Identifier | CTEP | |
| U10CA180868 | U.S. NIH Grant/Contract | View source |
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Inadequate accrual rate
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| Name | Class |
|---|---|
| NRG Oncology | OTHER |
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This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.
PRIMARY OBJECTIVES:
I. To assess whether ALK kinase domain mutations (G1202/C1156Y/I1171/L1196/ V1180/ F1174/compound mutation) associated with drug resistance are prognostic for objective response to subsequent ALK inhibitor therapy.
II. To assess whether subsequent pemetrexed based chemotherapy improves objective response comparing to ALK inhibitor therapy for no ALK mutation patients.
III. To evaluate objective responses of patients with specific genetic alterations (ALKL1198F/MET double mutation or high-level MET gene amplification) treated with crizotinib.
SECONDARY OBJECTIVES:
I. Progression-free survival (PFS). II. Duration of response (DOR). III. Overall survival (OS). IV. Intracranial objective response rate (ORR). V. Safety and tolerability.
CORRELATIVE SCIENCE OBJECTIVE:
I. Establish concordance between tumor and liquid biopsies.
OUTLINE:
Patients with a G1202R or G1202del mutation receive either lorlatinib orally (PO) once daily (QD) or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a C1156Y mutation receive either lorlatinib PO QD, brigatinib PO QD, or alectinib PO twice daily (BID). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a I1171 mutation receive either lorlatinib PO QD, ceritinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a L1196 mutation receive either lorlatinib PO QD, brigatinib PO QD, ensartinib PO QD, alectinib PO BID, or ceritinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a V1180 mutation receive either lorlatinib PO QD, brigatinib PO QD, or ceritinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a F1174 mutation receive either alectinib PO BID, lorlatinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with a compound mutation receive lorlatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with an ALK L1198F mutation alone or with another mutation, and patients with high level MET amplification receive crizotinib PO BID. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with no ALK-resistant mutations receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, or ensartinib PO QD, or pemetrexed intravenously (IV) over 10 minutes on day 1 and either cisplatin IV or carboplatin IV on day 1. ALK inhibitor cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Pemetrexed-based treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Maintenance treatment of pemetrexed may continue until disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALK L1198F mutation (alone or combination with ALK inhibitor) | Experimental | Patients with ALK L1198F mutation (alone or in combination with another ALK mutation) receive crizotinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| C1156Y | Experimental | Patients with Cy1156Y mutation receive either lorlatinib PO QD, alectinib PO BID, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| Compound mutation | Experimental | Patients with a compound mutation receive lorlatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| F1174 | Experimental | Patients with F1174 receive either lorlatinib PO QD, alectinib PO BID, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| G1202 (including G1202del and G1202R) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alectinib | Drug | Given PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria | ORR= number of subjects with best overall response (BOR) of complete or partial response (CR, PR) divided by number of evaluable subjects. BOR= best response recorded from start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.
ORR was to be compared using Fisher's exact test within each ALK inhibitor treatment arm (each mutation vs. no mutation) and also within the subset of subjects with no mutation comparing each experimental arm vs. pemetrexed. Due to early accrual closure (few subjects), only the number of subjects with BOR of CR or PR are provided, by mutation, no statistical testing. Analysis was to occur after each patient was potentially followed ≥ 24 weeks. | Baseline to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria | Progression-free survival time is defined as the time from second step registration to the date of the first disease progression / progressive disease (PD), death, or last known follow-up (censored). Progressive disease is defined as a 20% increase of target lesions and/or new lesion(s). Percentage of participants progression-free at a given time (PFS) was to be estimated by the Kaplan-Meier method. Median PFS and PFS at specific time points was to be reported, with 95% confidence intervals, for each mutation (or no mutation)/regimen combination. Due to early accrual closure resulting in few participants, only the number of participants who progressed or died, by mutation, with no statistical testing. |
| Measure | Description | Time Frame |
|---|---|---|
| Agreement of Biopsy Mutation and Circulating Free Deoxyribonucleic Acid (cfDNA) Mutation Results | For each mutation, the agreement of the biopsy result (present, absent, unavailable) and the cfDNA result (present, absent, unavailable) would be assessed. Agreement of cfDNA and biopsy results will be considered separately for MET amplification and for the gene mutations. This outcome measure was to be contingent upon FDA approval of the outcome measure analysis plan, which was not pursued due to the early accrual closure. |
Inclusion Criteria:
PRIOR TO STEP 1 REGISTRATION
Patients must have histologically or cytologically confirmed stage IV ALK-positive non-squamous non-small cell lung carcinoma (NSCLC) (includes M1a, M1b, M1c stage disease, American Joint Committee on Cancer [AJCC] 8th edition). ALK rearrangement must have been demonstrated by a Food and Drug Administration (FDA) approved assay (Vysis fluorescence in situ hybridization [FISH] or Ventana immunohistochemistry [IHC]) or by next generation sequencing (NGS)
Patient must be willing and able to undergo a fresh biopsy or if patient has a biopsy after progression on current tyrosine-kinase inhibitor (TKI) within 3 months of study enrollment (and has continued TKI for clinical benefit per treating physician) this tissue may be used. Must have sufficient tissue
Patient must have progressive disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after one second generation ALK inhibitor, including LDK378 (ceritinib), alectinib, ensartinib, and brigatinib (may not have received more than one second-generation ALK inhibitor). Patient may have received prior crizotinib; however, the second generation ALK inhibitor received must be the last treatment given prior to study enrollment
Prior chemotherapy is not allowed except for one prior cycle received at the time of original diagnosis of metastatic NSCLC with no evidence of disease progression following the cycle. NOTE: prior adjuvant or neoadjuvant chemotherapy is allowed if last dose was received more than 12 months prior to enrollment
The patient or a legally authorized representative must provide study-specific informed consent prior to Step 1 Registration
PRIOR TO STEP 2 REGISTRATION
Absolute neutrophil count (ANC) >= 1500 cells/mm^3 (within 28 days prior to step 2 registration)
Platelets >= 100,000 cells/mm^3 (within 28 days prior to step 2 registration)
Estimated creatinine clearance >= 60 mL/min by the Cockcroft Gault formula (within 28 days prior to step 2 registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's syndrome) (within 28 days prior to step 2 registration)
Aspartate aminotransferase (AST) =< 2.5 x ULN; =< 5 x ULN if liver metastases are present (within 28 days prior to step 2 registration)
Alanine aminotransferase (ALT) =< 2.5 x ULN; =< 5 x ULN if liver metastases are present (within 28 days prior to step 2 registration)
Patients with asymptomatic treated or untreated brain metastases are eligible. Treated brain metastases are eligible as long as patients have measurable disease outside the brain according to RECIST 1.1. Patients must be on a stable or decreasing dose of steroids for at least 7 days prior to step 2 registration. Anticonvulsants are allowed as long as the patient is neurologically stable and not deteriorating
Patients enrolled with asymptomatic brain metastases (mets) must have at least one measurable target extracranial lesion according to RECIST 1.1
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Acute effects of any prior therapy resolved to baseline severity or to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 (except for alopecia, hearing loss)
Not taking any medications that may interact with selected study medication based on stratification
Patients must be able to take oral medications (i.e. swallow whole tablets/capsules)
All females of childbearing potential must have a blood test or urine study within 14 days prior to Step 2 Registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jessica J Lin | NRG Oncology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CTCA at Western Regional Medical Center | Goodyear | Arizona | 85338 | United States | ||
| Mayo Clinic Hospital in Arizona |
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
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Tissue and blood submissions were required after first step registration, before second step registration (treatment assignment). Of 16 participants screened, 10 were assigned to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lorlatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, compound mutation*, or no mutations, can be assigned to receive lorlatinib. *Compound mutation = two or more resistance mutation excluding those with L1198F or L1189F/MET amplification = L1198F mutation alone or in combination, or no anaplastic lymphoma kinase (ALK) mutation but any MET amplification. Lorlatinib: 100 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 20, 2022 |
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Patients with G1202 (including G1202del and G1202R) receive either lorlatinib PO QD or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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| I1171 | Experimental | Patients with I1171 mutation receive either lorlatinib PO QD, ceritinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| L1196 (including L1196M) | Experimental | Patients with L1196 (including L1196M) mutation receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, or ensartinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| MET amplification | Experimental | Patients with MET amplification receive crizotinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| No ALK-resistance mutations | Experimental | Patients with no ALK-resistant mutations receive either lorlatinib PO QD, ceritinib PO QD, alectinib PO BID, brigatinib PO QD, ensartinib PO QD, or pemetrexed IV over 10 minutes on day 1 with or without either cisplatin IV or carboplatin IV on day 1. ALK inhibitor cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Pemetrexed-based treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Maintenance treatment of pemetrexed may continue until disease progression or unacceptable toxicity. |
|
| V1180 | Experimental | Patients with V1180 mutation receive either lorlatinib PO QD, ceritinib PO QD, or brigatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
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| Brigatinib | Drug | Given PO |
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| Carboplatin | Drug | Given IV |
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| Ceritinib | Drug | Given PO |
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| Cisplatin | Drug | Given IV |
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| Crizotinib | Drug | Given PO |
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| Ensartinib | Drug | Given PO |
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| Lorlatinib | Drug | Given PO |
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| Pemetrexed | Drug | Given IV |
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| Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1 | Duration of overall response (DOR) is defined as the time from the first occurrence of a documented BOR of CR or PR to the first date of recorded disease progression (PD) or death from any cause (whichever occurs first). BOR is the best response recorded from the start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.
Median DOR was to be estimated, with 95% confidence intervals, for each mutation/regimen combination using the Kaplan-Meier method. Due to early accrual closure resulting in few subjects, only the mean and range DOR are provided, by mutation, and no statistical testing was done. | Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| Overall Survival (OS) | Survival time is defined as the time from second step registration to the date of death, or last known follow-up (censored). Percentage of participants alive at a given time (OS) was to be estimated by the Kaplan-Meier method. Median OS and OS at specific time points was to be reported, with 95% confidence intervals, for each mutation/regimen combination. Due to early accrual closure resulting in few patients, only the number of participants who died are provided, by mutation, and no statistical testing was done. | Baseline to the date of death or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| Intracranial Objective Response Rate, Per Investigator Assessment Using RECIST v1.1 | Intracranial objective response rate (IORR) is defined as the number of participants with central nervous system (CNS) metastasis complete or partial response (CR, PR) divided by the number of evaluable participants with baseline CNS metastasis and no prior CNS radiation therapy. Participants who required additional treatment (for their non-cranial systemic disease) would be considered as non-responders (if they have not previously had an intracranial response).
IORR was to be estimated for each mutation/regimen combination, with the associated 95% confidence intervals (using Clapper-Pearson method). Due to early accrual closure resulting in few subjects, only the number of subjects with CR or PR are provided, by mutation, with no statistical testing. | Baseline to 24 weeks |
| Number of Participants by Highest Grade Adverse Event Reported | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. | Baseline to the date of last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| Baseline |
| Phoenix |
| Arizona |
| 85054 |
| United States |
| Mayo Clinic in Arizona | Scottsdale | Arizona | 85259 | United States |
| Mercy Hospital Fort Smith | Fort Smith | Arkansas | 72903 | United States |
| CHI Saint Vincent Cancer Center Hot Springs | Hot Springs | Arkansas | 71913 | United States |
| Kaiser Permanente-Anaheim | Anaheim | California | 92806 | United States |
| Kaiser Permanente-Deer Valley Medical Center | Antioch | California | 94531 | United States |
| Mission Hope Medical Oncology - Arroyo Grande | Arroyo Grande | California | 93420 | United States |
| Kaiser Permanente-Baldwin Park | Baldwin Park | California | 91706 | United States |
| Kaiser Permanente-Bellflower | Bellflower | California | 90706 | United States |
| Kaiser Permanente Dublin | Dublin | California | 94568 | United States |
| 21st Century Oncology - El Segundo | El Segundo | California | 90245 | United States |
| Kaiser Permanente-Fontana | Fontana | California | 92335 | United States |
| Kaiser Permanente-Fremont | Fremont | California | 94538 | United States |
| Fresno Cancer Center | Fresno | California | 93720 | United States |
| Kaiser Permanente-Fresno | Fresno | California | 93720 | United States |
| Kaiser Permanente South Bay | Harbor City | California | 90710 | United States |
| Kaiser Permanente-Irvine | Irvine | California | 92618 | United States |
| UC San Diego Moores Cancer Center | La Jolla | California | 92093 | United States |
| Loma Linda University Medical Center | Loma Linda | California | 92354 | United States |
| Kaiser Permanente Los Angeles Medical Center | Los Angeles | California | 90027 | United States |
| Kaiser Permanente West Los Angeles | Los Angeles | California | 90034 | United States |
| Kaiser Permanente-Modesto | Modesto | California | 95356 | United States |
| Kaiser Permanente Oakland-Broadway | Oakland | California | 94611 | United States |
| Kaiser Permanente-Oakland | Oakland | California | 94611 | United States |
| Kaiser Permanente-Ontario | Ontario | California | 91761 | United States |
| Kaiser Permanente - Panorama City | Panorama City | California | 91402 | United States |
| Kaiser Permanente-Rancho Cordova Cancer Center | Rancho Cordova | California | 95670 | United States |
| Kaiser Permanente-Redwood City | Redwood City | California | 94063 | United States |
| Kaiser Permanente-Richmond | Richmond | California | 94801 | United States |
| Kaiser Permanente-Riverside | Riverside | California | 92505 | United States |
| Rohnert Park Cancer Center | Rohnert Park | California | 94928 | United States |
| Kaiser Permanente-Roseville | Roseville | California | 95661 | United States |
| The Permanente Medical Group-Roseville Radiation Oncology | Roseville | California | 95678 | United States |
| Kaiser Permanente Downtown Commons | Sacramento | California | 95814 | United States |
| Kaiser Permanente-South Sacramento | Sacramento | California | 95823 | United States |
| South Sacramento Cancer Center | Sacramento | California | 95823 | United States |
| Kaiser Permanente Sacramento Medical Center | Sacramento | California | 95825 | United States |
| Kaiser Permanente-San Diego Mission | San Diego | California | 92108 | United States |
| Kaiser Permanente-San Diego Zion | San Diego | California | 92120 | United States |
| Kaiser Permanente-San Francisco | San Francisco | California | 94115 | United States |
| Kaiser Permanente-Santa Teresa-San Jose | San Jose | California | 95119 | United States |
| Kaiser Permanente San Leandro | San Leandro | California | 94577 | United States |
| Pacific Central Coast Health Center-San Luis Obispo | San Luis Obispo | California | 93401 | United States |
| Kaiser Permanente-San Marcos | San Marcos | California | 92078 | United States |
| Kaiser Permanente-San Rafael | San Rafael | California | 94903 | United States |
| Kaiser San Rafael-Gallinas | San Rafael | California | 94903 | United States |
| Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | 95051 | United States |
| Mission Hope Medical Oncology - Santa Maria | Santa Maria | California | 93444 | United States |
| Kaiser Permanente-Santa Rosa | Santa Rosa | California | 95403 | United States |
| Kaiser Permanente Cancer Treatment Center | South San Francisco | California | 94080 | United States |
| Kaiser Permanente-South San Francisco | South San Francisco | California | 94080 | United States |
| Kaiser Permanente-Stockton | Stockton | California | 95210 | United States |
| Kaiser Permanente Medical Center-Vacaville | Vacaville | California | 95688 | United States |
| Kaiser Permanente-Vallejo | Vallejo | California | 94589 | United States |
| Kaiser Permanente-Walnut Creek | Walnut Creek | California | 94596 | United States |
| Kaiser Permanente-Woodland Hills | Woodland Hills | California | 91367 | United States |
| UCHealth University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
| Penrose-Saint Francis Healthcare | Colorado Springs | Colorado | 80907 | United States |
| Rocky Mountain Cancer Centers-Penrose | Colorado Springs | Colorado | 80907 | United States |
| UCHealth Memorial Hospital Central | Colorado Springs | Colorado | 80909 | United States |
| Memorial Hospital North | Colorado Springs | Colorado | 80920 | United States |
| AdventHealth Porter | Denver | Colorado | 80210 | United States |
| CommonSpirit Cancer Center Mercy | Durango | Colorado | 81301 | United States |
| Mercy Medical Center | Durango | Colorado | 81301 | United States |
| Mountain Blue Cancer Care Center | Golden | Colorado | 80401 | United States |
| Rocky Mountain Cancer Centers-Lakewood | Lakewood | Colorado | 80228 | United States |
| Saint Anthony Hospital | Lakewood | Colorado | 80228 | United States |
| AdventHealth Littleton | Littleton | Colorado | 80122 | United States |
| Longmont United Hospital | Longmont | Colorado | 80501 | United States |
| Rocky Mountain Cancer Centers-Longmont | Longmont | Colorado | 80501 | United States |
| AdventHealth Parker | Parker | Colorado | 80138 | United States |
| Rocky Mountain Cancer Centers-Parker | Parker | Colorado | 80138 | United States |
| Saint Mary Corwin Medical Center | Pueblo | Colorado | 81004 | United States |
| Rocky Mountain Cancer Centers - Pueblo | Pueblo | Colorado | 81008 | United States |
| Rocky Mountain Cancer Centers-Thornton | Thornton | Colorado | 80260 | United States |
| Beebe Medical Center | Lewes | Delaware | 19958 | United States |
| Beebe South Coastal Health Campus | Millville | Delaware | 19967 | United States |
| Delaware Clinical and Laboratory Physicians PA | Newark | Delaware | 19713 | United States |
| Helen F Graham Cancer Center | Newark | Delaware | 19713 | United States |
| Medical Oncology Hematology Consultants PA | Newark | Delaware | 19713 | United States |
| Christiana Care Health System-Christiana Hospital | Newark | Delaware | 19718 | United States |
| Beebe Health Campus | Rehoboth Beach | Delaware | 19971 | United States |
| TidalHealth Nanticoke / Allen Cancer Center | Seaford | Delaware | 19973 | United States |
| Christiana Care Health System-Wilmington Hospital | Wilmington | Delaware | 19801 | United States |
| Sibley Memorial Hospital | Washington D.C. | District of Columbia | 20016 | United States |
| GenesisCare USA - Aventura FP | Aventura | Florida | 33180 | United States |
| GenesisCare USA - Boca Raton FP02 | Boca Raton | Florida | 33428 | United States |
| GenesisCare USA - Boca Ration FP06 | Boca Raton | Florida | 33431 | United States |
| Holy Cross Hospital | Fort Lauderdale | Florida | 33308 | United States |
| Mayo Clinic in Florida | Jacksonville | Florida | 32224-9980 | United States |
| GenesisCare USA - Key West | Key West | Florida | 33040 | United States |
| GenesisCare USA - Lakewood Ranch | Lakewood Rch | Florida | 34202 | United States |
| GenesisCare USA - Palm Beach Gardens | Palm Beach Gardens | Florida | 33410 | United States |
| GenesisCare USA - Plantation | Plantation | Florida | 33324 | United States |
| Good Samaritan Medical Center | West Palm Beach | Florida | 33401 | United States |
| Grady Health System | Atlanta | Georgia | 30303 | United States |
| Emory University Hospital Midtown | Atlanta | Georgia | 30308 | United States |
| Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| Emory Saint Joseph's Hospital | Atlanta | Georgia | 30342 | United States |
| Northside Hospital | Atlanta | Georgia | 30342 | United States |
| Northside Hospital - Duluth | Duluth | Georgia | 30096 | United States |
| Emory Johns Creek Hospital | Johns Creek | Georgia | 30097 | United States |
| Northside Hospital - Gwinnett | Lawrenceville | Georgia | 30046 | United States |
| CTCA at Southeastern Regional Medical Center | Newnan | Georgia | 30265 | United States |
| Suburban Hematology Oncology Associates - Snellville | Snellville | Georgia | 30078 | United States |
| Hawaii Cancer Care Inc - Waterfront Plaza | Honolulu | Hawaii | 96813 | United States |
| Island Urology | Honolulu | Hawaii | 96813 | United States |
| Queen's Cancer Cenrer - POB I | Honolulu | Hawaii | 96813 | United States |
| Queen's Medical Center | Honolulu | Hawaii | 96813 | United States |
| Straub Clinic and Hospital | Honolulu | Hawaii | 96813 | United States |
| University of Hawaii Cancer Center | Honolulu | Hawaii | 96813 | United States |
| Hawaii Cancer Care Inc-Liliha | Honolulu | Hawaii | 96817 | United States |
| Kuakini Medical Center | Honolulu | Hawaii | 96817 | United States |
| Queen's Cancer Center - Kuakini | Honolulu | Hawaii | 96817 | United States |
| The Cancer Center of Hawaii-Liliha | Honolulu | Hawaii | 96817 | United States |
| Kaiser Permanente Moanalua Medical Center | Honolulu | Hawaii | 96819 | United States |
| Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | 96826 | United States |
| Wilcox Memorial Hospital and Kauai Medical Clinic | Lihue | Hawaii | 96766 | United States |
| Hawaii Cancer Care - Westridge | ‘Aiea | Hawaii | 96701 | United States |
| Pali Momi Medical Center | ‘Aiea | Hawaii | 96701 | United States |
| Queen's Cancer Center - Pearlridge | ‘Aiea | Hawaii | 96701 | United States |
| The Cancer Center of Hawaii-Pali Momi | ‘Aiea | Hawaii | 96701 | United States |
| Saint Alphonsus Cancer Care Center-Boise | Boise | Idaho | 83706 | United States |
| Saint Alphonsus Cancer Care Center-Caldwell | Caldwell | Idaho | 83605 | United States |
| Kootenai Health - Coeur d'Alene | Coeur d'Alene | Idaho | 83814 | United States |
| Walter Knox Memorial Hospital | Emmett | Idaho | 83617 | United States |
| Idaho Urologic Institute-Meridian | Meridian | Idaho | 83642 | United States |
| Saint Alphonsus Cancer Care Center-Nampa | Nampa | Idaho | 83687 | United States |
| Kootenai Clinic Cancer Services - Post Falls | Post Falls | Idaho | 83854 | United States |
| Kootenai Clinic Cancer Services - Sandpoint | Sandpoint | Idaho | 83864 | United States |
| Rush-Copley Medical Center | Aurora | Illinois | 60504 | United States |
| Illinois CancerCare-Bloomington | Bloomington | Illinois | 61704 | United States |
| Illinois CancerCare-Canton | Canton | Illinois | 61520 | United States |
| Memorial Hospital of Carbondale | Carbondale | Illinois | 62902 | United States |
| SIH Cancer Institute | Carterville | Illinois | 62918 | United States |
| Illinois CancerCare-Carthage | Carthage | Illinois | 62321 | United States |
| Centralia Oncology Clinic | Centralia | Illinois | 62801 | United States |
| University of Illinois | Chicago | Illinois | 60612 | United States |
| Carle at The Riverfront | Danville | Illinois | 61832 | United States |
| Cancer Care Specialists of Illinois - Decatur | Decatur | Illinois | 62526 | United States |
| Decatur Memorial Hospital | Decatur | Illinois | 62526 | United States |
| Illinois CancerCare-Dixon | Dixon | Illinois | 61021 | United States |
| Carle Physician Group-Effingham | Effingham | Illinois | 62401 | United States |
| Crossroads Cancer Center | Effingham | Illinois | 62401 | United States |
| Illinois CancerCare-Eureka | Eureka | Illinois | 61530 | United States |
| NorthShore University HealthSystem-Evanston Hospital | Evanston | Illinois | 60201 | United States |
| Illinois CancerCare-Galesburg | Galesburg | Illinois | 61401 | United States |
| Western Illinois Cancer Treatment Center | Galesburg | Illinois | 61401 | United States |
| NorthShore University HealthSystem-Glenbrook Hospital | Glenview | Illinois | 60026 | United States |
| NorthShore University HealthSystem-Highland Park Hospital | Highland Park | Illinois | 60035 | United States |
| Illinois CancerCare-Kewanee Clinic | Kewanee | Illinois | 61443 | United States |
| Illinois CancerCare-Macomb | Macomb | Illinois | 61455 | United States |
| Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois | 61938 | United States |
| SSM Health Good Samaritan | Mount Vernon | Illinois | 62864 | United States |
| Cancer Care Center of O'Fallon | O'Fallon | Illinois | 62269 | United States |
| Illinois CancerCare-Ottawa Clinic | Ottawa | Illinois | 61350 | United States |
| Illinois CancerCare-Pekin | Pekin | Illinois | 61554 | United States |
| Illinois CancerCare-Peoria | Peoria | Illinois | 61615 | United States |
| Methodist Medical Center of Illinois | Peoria | Illinois | 61636 | United States |
| Illinois CancerCare-Peru | Peru | Illinois | 61354 | United States |
| Valley Radiation Oncology | Peru | Illinois | 61354 | United States |
| Illinois CancerCare-Princeton | Princeton | Illinois | 61356 | United States |
| Southern Illinois University School of Medicine | Springfield | Illinois | 62702 | United States |
| Springfield Clinic | Springfield | Illinois | 62702 | United States |
| Springfield Memorial Hospital | Springfield | Illinois | 62781 | United States |
| Southwest Illinois Health Services LLP | Swansea | Illinois | 62226 | United States |
| Carle Cancer Center | Urbana | Illinois | 61801 | United States |
| The Carle Foundation Hospital | Urbana | Illinois | 61801 | United States |
| Rush-Copley Healthcare Center | Yorkville | Illinois | 60560 | United States |
| Indiana University/Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Reid Health | Richmond | Indiana | 47374 | United States |
| Mary Greeley Medical Center | Ames | Iowa | 50010 | United States |
| McFarland Clinic - Ames | Ames | Iowa | 50010 | United States |
| McFarland Clinic - Boone | Boone | Iowa | 50036 | United States |
| Mercy Cancer Center-West Lakes | Clive | Iowa | 50325 | United States |
| UI Health Care Mission Cancer and Blood - West Des Moines Clinic | Clive | Iowa | 50325 | United States |
| Alegent Health Mercy Hospital | Council Bluffs | Iowa | 51503 | United States |
| Greater Regional Medical Center | Creston | Iowa | 50801 | United States |
| Mercy Medical Center - Des Moines | Des Moines | Iowa | 50314 | United States |
| UI Health Care Mission Cancer and Blood - Laurel Clinic | Des Moines | Iowa | 50314 | United States |
| McFarland Clinic - Trinity Cancer Center | Fort Dodge | Iowa | 50501 | United States |
| McFarland Clinic - Jefferson | Jefferson | Iowa | 50129 | United States |
| McFarland Clinic - Marshalltown | Marshalltown | Iowa | 50158 | United States |
| Mercy Medical Center-West Lakes | West Des Moines | Iowa | 50266 | United States |
| Flaget Memorial Hospital | Bardstown | Kentucky | 40004 | United States |
| Commonwealth Cancer Center-Corbin | Corbin | Kentucky | 40701 | United States |
| Saint Joseph Radiation Oncology Resource Center | Lexington | Kentucky | 40504 | United States |
| Saint Joseph Hospital East | Lexington | Kentucky | 40509 | United States |
| Saint Joseph London | London | Kentucky | 40741 | United States |
| Jewish Hospital | Louisville | Kentucky | 40202 | United States |
| Saints Mary and Elizabeth Hospital | Louisville | Kentucky | 40215 | United States |
| UofL Health Medical Center Northeast | Louisville | Kentucky | 40245 | United States |
| Jewish Hospital Medical Center South | Shepherdsville | Kentucky | 40165 | United States |
| Eastern Maine Medical Center | Bangor | Maine | 04401 | United States |
| Lafayette Family Cancer Center-EMMC | Brewer | Maine | 04412 | United States |
| Saint Agnes Hospital | Baltimore | Maryland | 21229 | United States |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States |
| Massachusetts General Hospital Cancer Center | Boston | Massachusetts | 02114 | United States |
| Mercy Medical Center | Springfield | Massachusetts | 01104 | United States |
| Trinity Health Saint Joseph Mercy Hospital Ann Arbor | Ann Arbor | Michigan | 48106 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Brighton | Brighton | Michigan | 48114 | United States |
| Trinity Health Medical Center - Brighton | Brighton | Michigan | 48114 | United States |
| Henry Ford Cancer Institute-Downriver | Brownstown | Michigan | 48183 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Canton | Canton | Michigan | 48188 | United States |
| Trinity Health Medical Center - Canton | Canton | Michigan | 48188 | United States |
| Caro Cancer Center | Caro | Michigan | 48723 | United States |
| Chelsea Hospital | Chelsea | Michigan | 48118 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Chelsea | Michigan | 48118 | United States |
| Hematology Oncology Consultants-Clarkston | Clarkston | Michigan | 48346 | United States |
| Michigan Healthcare Professionals Clarkston | Clarkston | Michigan | 48346 | United States |
| Newland Medical Associates-Clarkston | Clarkston | Michigan | 48346 | United States |
| Henry Ford Macomb Hospital-Clinton Township | Clinton Township | Michigan | 48038 | United States |
| Henry Ford Medical Center-Fairlane | Dearborn | Michigan | 48126 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Henry Ford Health Saint John Hospital | Detroit | Michigan | 48236 | United States |
| Henry Ford River District Hospital | East China Township | Michigan | 48054 | United States |
| Michigan Healthcare Professionals Farmington | Farmington Hills | Michigan | 48334 | United States |
| Cancer Hematology Centers - Flint | Flint | Michigan | 48503 | United States |
| Genesee Hematology Oncology PC | Flint | Michigan | 48503 | United States |
| Genesys Hurley Cancer Institute | Flint | Michigan | 48503 | United States |
| Hurley Medical Center | Flint | Michigan | 48503 | United States |
| Henry Ford Saint John Hospital - Academic | Grosse Pointe Woods | Michigan | 48236 | United States |
| Henry Ford Saint John Hospital - Breast | Grosse Pointe Woods | Michigan | 48236 | United States |
| Henry Ford Saint John Hospital - Van Elslander | Grosse Pointe Woods | Michigan | 48236 | United States |
| Allegiance Health | Jackson | Michigan | 49201 | United States |
| University of Michigan Health - Sparrow Lansing | Lansing | Michigan | 48912 | United States |
| Hope Cancer Clinic | Livonia | Michigan | 48154 | United States |
| Trinity Health Saint Mary Mercy Livonia Hospital | Livonia | Michigan | 48154 | United States |
| Henry Ford Saint John Hospital - Macomb Medical | Macomb | Michigan | 48044 | United States |
| Henry Ford Warren Hospital - Breast Macomb | Macomb | Michigan | 48044 | United States |
| Michigan Healthcare Professionals Macomb | Macomb | Michigan | 48044 | United States |
| Michigan Healthcare Professionals Madison Heights | Madison Heights | Michigan | 48071 | United States |
| Saint Mary's Oncology/Hematology Associates of Marlette | Marlette | Michigan | 48453 | United States |
| Henry Ford Medical Center-Columbus | Novi | Michigan | 48377 | United States |
| Hope Cancer Center | Pontiac | Michigan | 48341 | United States |
| Michigan Healthcare Professionals Pontiac | Pontiac | Michigan | 48341 | United States |
| Newland Medical Associates-Pontiac | Pontiac | Michigan | 48341 | United States |
| Trinity Health Saint Joseph Mercy Oakland Hospital | Pontiac | Michigan | 48341 | United States |
| Henry Ford Rochester Hospital | Rochester Hills | Michigan | 48309 | United States |
| MyMichigan Medical Center Saginaw | Saginaw | Michigan | 48601 | United States |
| Oncology Hematology Associates of Saginaw Valley PC | Saginaw | Michigan | 48604 | United States |
| Henry Ford Macomb Health Center - Shelby Township | Shelby | Michigan | 48315 | United States |
| Bhadresh Nayak MD PC-Sterling Heights | Sterling Heights | Michigan | 48312 | United States |
| MyMichigan Medical Center Tawas | Tawas City | Michigan | 48764 | United States |
| Michigan Healthcare Professionals Troy | Troy | Michigan | 48098 | United States |
| Advanced Breast Care Center PLLC | Warren | Michigan | 48088 | United States |
| Henry Ford Health Warren Hospital | Warren | Michigan | 48093 | United States |
| Henry Ford Madison Heights Hospital - Breast | Warren | Michigan | 48093 | United States |
| Henry Ford Warren Hospital - GLCMS | Warren | Michigan | 48093 | United States |
| Macomb Hematology Oncology PC | Warren | Michigan | 48093 | United States |
| Henry Ford West Bloomfield Hospital | West Bloomfield | Michigan | 48322 | United States |
| Saint Mary's Oncology/Hematology Associates of West Branch | West Branch | Michigan | 48661 | United States |
| Huron Gastroenterology PC | Ypsilanti | Michigan | 48106 | United States |
| Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus | Ypsilanti | Michigan | 48197 | United States |
| Riverwood Healthcare Center | Aitkin | Minnesota | 56431 | United States |
| Sanford Joe Lueken Cancer Center | Bemidji | Minnesota | 56601 | United States |
| Essentia Health Saint Joseph's Medical Center | Brainerd | Minnesota | 56401 | United States |
| Fairview Ridges Hospital | Burnsville | Minnesota | 55337 | United States |
| Minnesota Oncology - Burnsville | Burnsville | Minnesota | 55337 | United States |
| Cambridge Medical Center | Cambridge | Minnesota | 55008 | United States |
| Mercy Hospital | Coon Rapids | Minnesota | 55433 | United States |
| Essentia Health - Deer River Clinic | Deer River | Minnesota | 56636 | United States |
| Essentia Health Saint Mary's - Detroit Lakes Clinic | Detroit Lakes | Minnesota | 56501 | United States |
| Essentia Health Cancer Center | Duluth | Minnesota | 55805 | United States |
| Essentia Health Saint Mary's Medical Center | Duluth | Minnesota | 55805 | United States |
| Miller-Dwan Hospital | Duluth | Minnesota | 55805 | United States |
| Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States |
| Lake Region Healthcare Corporation-Cancer Care | Fergus Falls | Minnesota | 56537 | United States |
| Essentia Health - Fosston | Fosston | Minnesota | 56542 | United States |
| Unity Hospital | Fridley | Minnesota | 55432 | United States |
| Essentia Health Hibbing Clinic | Hibbing | Minnesota | 55746 | United States |
| Fairview Clinics and Surgery Center Maple Grove | Maple Grove | Minnesota | 55369 | United States |
| Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota | 55109 | United States |
| Saint John's Hospital - Healtheast | Maplewood | Minnesota | 55109 | United States |
| Abbott-Northwestern Hospital | Minneapolis | Minnesota | 55407 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| Health Partners Inc | Minneapolis | Minnesota | 55454 | United States |
| Monticello Cancer Center | Monticello | Minnesota | 55362 | United States |
| New Ulm Medical Center | New Ulm | Minnesota | 56073 | United States |
| Essentia Health - Park Rapids | Park Rapids | Minnesota | 56470 | United States |
| Fairview Northland Medical Center | Princeton | Minnesota | 55371 | United States |
| North Memorial Medical Health Center | Robbinsdale | Minnesota | 55422 | United States |
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota | 55416 | United States |
| Regions Hospital | Saint Paul | Minnesota | 55101 | United States |
| United Hospital | Saint Paul | Minnesota | 55102 | United States |
| Essentia Health Sandstone | Sandstone | Minnesota | 55072 | United States |
| Saint Francis Regional Medical Center | Shakopee | Minnesota | 55379 | United States |
| Lakeview Hospital | Stillwater | Minnesota | 55082 | United States |
| Sanford Thief River Falls Medical Center | Thief River Falls | Minnesota | 56701 | United States |
| Essentia Health Virginia Clinic | Virginia | Minnesota | 55792 | United States |
| Ridgeview Medical Center | Waconia | Minnesota | 55387 | United States |
| Rice Memorial Hospital | Willmar | Minnesota | 56201 | United States |
| Minnesota Oncology Hematology PA-Woodbury | Woodbury | Minnesota | 55125 | United States |
| Sanford Cancer Center Worthington | Worthington | Minnesota | 56187 | United States |
| Fairview Lakes Medical Center | Wyoming | Minnesota | 55092 | United States |
| Baptist Memorial Hospital and Cancer Center-Desoto | Southhaven | Mississippi | 38671 | United States |
| Mercy Oncology and Hematology - Clayton-Clarkson | Ballwin | Missouri | 63011 | United States |
| Parkland Health Center-Bonne Terre | Bonne Terre | Missouri | 63628 | United States |
| Cox Cancer Center Branson | Branson | Missouri | 65616 | United States |
| Mercy Cancer Center - Cape Girardeau | Cape Girardeau | Missouri | 63703 | United States |
| Saint Francis Medical Center | Cape Girardeau | Missouri | 63703 | United States |
| Siteman Cancer Center at Saint Peters Hospital | City of Saint Peters | Missouri | 63376 | United States |
| Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri | 63141 | United States |
| Parkland Health Center - Farmington | Farmington | Missouri | 63640 | United States |
| MU Health Care Goldschmidt Cancer Center | Jefferson City | Missouri | 65109 | United States |
| Freeman Health System | Joplin | Missouri | 64804 | United States |
| Mercy Hospital Joplin | Joplin | Missouri | 64804 | United States |
| Mercy Clinic-Rolla-Cancer and Hematology | Rolla | Missouri | 65401 | United States |
| Phelps Health Delbert Day Cancer Institute | Rolla | Missouri | 65401 | United States |
| Heartland Regional Medical Center | Saint Joseph | Missouri | 64506 | United States |
| Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri | 63670 | United States |
| Mercy Hospital Springfield | Springfield | Missouri | 65804 | United States |
| CoxHealth South Hospital | Springfield | Missouri | 65807 | United States |
| Mercy Infusion Center - Chippewa | St Louis | Missouri | 63109 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Mercy Hospital South | St Louis | Missouri | 63128 | United States |
| Siteman Cancer Center-South County | St Louis | Missouri | 63129 | United States |
| Missouri Baptist Medical Center | St Louis | Missouri | 63131 | United States |
| Siteman Cancer Center at Christian Hospital | St Louis | Missouri | 63136 | United States |
| Mercy Hospital Saint Louis | St Louis | Missouri | 63141 | United States |
| Missouri Baptist Sullivan Hospital | Sullivan | Missouri | 63080 | United States |
| BJC Outpatient Center at Sunset Hills | Sunset Hills | Missouri | 63127 | United States |
| Mercy Hospital Washington | Washington | Missouri | 63090 | United States |
| Community Hospital of Anaconda | Anaconda | Montana | 59711 | United States |
| Billings Clinic Cancer Center | Billings | Montana | 59101 | United States |
| Bozeman Health Deaconess Hospital | Bozeman | Montana | 59715 | United States |
| Benefis Sletten Cancer Institute | Great Falls | Montana | 59405 | United States |
| Great Falls Clinic | Great Falls | Montana | 59405 | United States |
| Saint Peter's Community Hospital | Helena | Montana | 59601 | United States |
| Logan Health Medical Center | Kalispell | Montana | 59901 | United States |
| Community Medical Center | Missoula | Montana | 59804 | United States |
| Nebraska Cancer Specialists/Oncology Hematology West PC | Grand Island | Nebraska | 68803 | United States |
| Fred and Pamela Buffett Cancer Center - Kearney | Kearney | Nebraska | 68845 | United States |
| CHI Health Good Samaritan | Kearney | Nebraska | 68847 | United States |
| Saint Elizabeth Regional Medical Center | Lincoln | Nebraska | 68510 | United States |
| Nebraska Methodist Hospital | Omaha | Nebraska | 68114 | United States |
| Alegent Health Immanuel Medical Center | Omaha | Nebraska | 68122 | United States |
| Hematology and Oncology Consultants PC | Omaha | Nebraska | 68122 | United States |
| Alegent Health Bergan Mercy Medical Center | Omaha | Nebraska | 68124 | United States |
| Alegent Health Lakeside Hospital | Omaha | Nebraska | 68130 | United States |
| Creighton University Medical Center | Omaha | Nebraska | 68131 | United States |
| Midlands Community Hospital | Papillion | Nebraska | 68046 | United States |
| Mount Sinai Chelsea | New York | New York | 10011 | United States |
| Mount Sinai Hospital | New York | New York | 10029 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| ECU Health Oncology Kenansville | Kenansville | North Carolina | 28349 | United States |
| ECU Health Oncology Kinston | Kinston | North Carolina | 28501 | United States |
| ECU Health Oncology Richlands | Richlands | North Carolina | 28574 | United States |
| Sanford Bismarck Medical Center | Bismarck | North Dakota | 58501 | United States |
| Essentia Health Cancer Center-South University Clinic | Fargo | North Dakota | 58103 | United States |
| Sanford South University Medical Center | Fargo | North Dakota | 58103 | United States |
| Southpointe-Sanford Medical Center Fargo | Fargo | North Dakota | 58103 | United States |
| Sanford Medical Center Fargo | Fargo | North Dakota | 58104 | United States |
| Sanford Broadway Medical Center | Fargo | North Dakota | 58122 | United States |
| Sanford Roger Maris Cancer Center | Fargo | North Dakota | 58122 | United States |
| Essentia Health - Jamestown Clinic | Jamestown | North Dakota | 58401 | United States |
| Indu and Raj Soin Medical Center | Beavercreek | Ohio | 45431 | United States |
| Strecker Cancer Center-Belpre | Belpre | Ohio | 45714 | United States |
| Saint Elizabeth Boardman Hospital | Boardman | Ohio | 44512 | United States |
| Dayton Physicians LLC-Miami Valley South | Centerville | Ohio | 45459 | United States |
| Miami Valley Hospital South | Centerville | Ohio | 45459 | United States |
| Adena Regional Medical Center | Chillicothe | Ohio | 45601 | United States |
| University of Cincinnati Cancer Center-UC Medical Center | Cincinnati | Ohio | 45219 | United States |
| Good Samaritan Hospital - Cincinnati | Cincinnati | Ohio | 45220 | United States |
| Oncology Hematology Care Inc-Kenwood | Cincinnati | Ohio | 45236 | United States |
| Bethesda North Hospital | Cincinnati | Ohio | 45242 | United States |
| TriHealth Cancer Institute-Westside | Cincinnati | Ohio | 45247 | United States |
| TriHealth Cancer Institute-Anderson | Cincinnati | Ohio | 45255 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Ohio State University Comprehensive Cancer Center | Columbus | Ohio | 43210 | United States |
| Mount Carmel East Hospital | Columbus | Ohio | 43213 | United States |
| Columbus Oncology and Hematology Associates Inc | Columbus | Ohio | 43214 | United States |
| Riverside Methodist Hospital | Columbus | Ohio | 43214 | United States |
| Grant Medical Center | Columbus | Ohio | 43215 | United States |
| The Mark H Zangmeister Center | Columbus | Ohio | 43219 | United States |
| Mount Carmel Health Center West | Columbus | Ohio | 43222 | United States |
| Doctors Hospital | Columbus | Ohio | 43228 | United States |
| Good Samaritan Hospital - Dayton | Dayton | Ohio | 45406 | United States |
| Miami Valley Hospital | Dayton | Ohio | 45409 | United States |
| Dayton Physician LLC - Englewood | Dayton | Ohio | 45415 | United States |
| Miami Valley Hospital North | Dayton | Ohio | 45415 | United States |
| Delaware Health Center-Grady Cancer Center | Delaware | Ohio | 43015 | United States |
| Grady Memorial Hospital | Delaware | Ohio | 43015 | United States |
| Dublin Methodist Hospital | Dublin | Ohio | 43016 | United States |
| Armes Family Cancer Center | Findlay | Ohio | 45840 | United States |
| Blanchard Valley Hospital | Findlay | Ohio | 45840 | United States |
| Orion Cancer Care | Findlay | Ohio | 45840 | United States |
| Atrium Medical Center-Middletown Regional Hospital | Franklin | Ohio | 45005-1066 | United States |
| Dayton Physicians LLC-Atrium | Franklin | Ohio | 45005 | United States |
| Central Ohio Breast and Endocrine Surgery | Gahanna | Ohio | 43230 | United States |
| Dayton Physicians LLC-Wayne | Greenville | Ohio | 45331 | United States |
| Wayne Hospital | Greenville | Ohio | 45331 | United States |
| Mount Carmel Grove City Hospital | Grove City | Ohio | 43123 | United States |
| Greater Dayton Cancer Center | Kettering | Ohio | 45409 | United States |
| First Dayton Cancer Care | Kettering | Ohio | 45420 | United States |
| Kettering Medical Center | Kettering | Ohio | 45429 | United States |
| Fairfield Medical Center | Lancaster | Ohio | 43130 | United States |
| OhioHealth Mansfield Hospital | Mansfield | Ohio | 44903 | United States |
| Marietta Memorial Hospital | Marietta | Ohio | 45750 | United States |
| OhioHealth Marion General Hospital | Marion | Ohio | 43302 | United States |
| Knox Community Hospital | Mount Vernon | Ohio | 43050 | United States |
| Licking Memorial Hospital | Newark | Ohio | 43055 | United States |
| Newark Radiation Oncology | Newark | Ohio | 43055 | United States |
| Southern Ohio Medical Center | Portsmouth | Ohio | 45662 | United States |
| Springfield Regional Cancer Center | Springfield | Ohio | 45504 | United States |
| Springfield Regional Medical Center | Springfield | Ohio | 45504 | United States |
| Dayton Physicians LLC - Troy | Troy | Ohio | 45373 | United States |
| Upper Valley Medical Center | Troy | Ohio | 45373 | United States |
| Saint Joseph Warren Hospital | Warren | Ohio | 44484 | United States |
| University of Cincinnati Cancer Center-West Chester | West Chester | Ohio | 45069 | United States |
| Saint Ann's Hospital | Westerville | Ohio | 43081 | United States |
| Saint Elizabeth Youngstown Hospital | Youngstown | Ohio | 44501 | United States |
| Genesis Healthcare System Cancer Care Center | Zanesville | Ohio | 43701 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Mercy Hospital Oklahoma City | Oklahoma City | Oklahoma | 73120 | United States |
| Cancer Treatment Centers of America | Tulsa | Oklahoma | 74133 | United States |
| Oklahoma Cancer Specialists and Research Institute-Tulsa | Tulsa | Oklahoma | 74146 | United States |
| Saint Alphonsus Cancer Care Center-Baker City | Baker City | Oregon | 97814 | United States |
| Legacy Mount Hood Medical Center | Gresham | Oregon | 97030 | United States |
| Saint Alphonsus Cancer Care Center-Ontario | Ontario | Oregon | 97914 | United States |
| Legacy Good Samaritan Hospital and Medical Center | Portland | Oregon | 97210 | United States |
| Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | 18103 | United States |
| UPMC Altoona | Altoona | Pennsylvania | 16601 | United States |
| UPMC Cancer Center-Bethel Park | Bethel Park | Pennsylvania | 15102 | United States |
| Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | 18017 | United States |
| Bryn Mawr Hospital | Bryn Mawr | Pennsylvania | 19010 | United States |
| Christiana Care Health System-Concord Health Center | Chadds Ford | Pennsylvania | 19317 | United States |
| Geisinger Medical Center | Danville | Pennsylvania | 17822 | United States |
| Pocono Medical Center | East Stroudsburg | Pennsylvania | 18301 | United States |
| UPMC Pinnacle Cancer Center/Community Osteopathic Campus | Harrisburg | Pennsylvania | 17109 | United States |
| Geisinger Medical Center-Cancer Center Hazleton | Hazleton | Pennsylvania | 18201 | United States |
| Lehigh Valley Hospital-Hazleton | Hazleton | Pennsylvania | 18201 | United States |
| Geisinger Medical Oncology-Lewisburg | Lewisburg | Pennsylvania | 17837 | United States |
| Lewistown Hospital | Lewistown | Pennsylvania | 17044 | United States |
| UPMC Cancer Center at UPMC McKeesport | McKeesport | Pennsylvania | 15132 | United States |
| Riddle Memorial Hospital | Media | Pennsylvania | 19063 | United States |
| Arnold Palmer Cancer Center Medical Oncology Norwin | N. Huntingdon | Pennsylvania | 15642 | United States |
| Paoli Memorial Hospital | Paoli | Pennsylvania | 19301 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Eastern Regional Medical Center | Philadelphia | Pennsylvania | 19124 | United States |
| Oncology Hematology Association | Pittsburgh | Pennsylvania | 15215 | United States |
| UPMC-Mercy Hospital | Pittsburgh | Pennsylvania | 15219 | United States |
| University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | 15232 | United States |
| UPMC-Passavant Hospital | Pittsburgh | Pennsylvania | 15237 | United States |
| Saint Clair Hospital | Pittsburgh | Pennsylvania | 15243 | United States |
| Geisinger Cancer Services-Pottsville | Pottsville | Pennsylvania | 17901 | United States |
| Community Medical Center | Scranton | Pennsylvania | 18510 | United States |
| Geisinger Medical Oncology-Selinsgrove | Selinsgrove | Pennsylvania | 17870 | United States |
| Geisinger Medical Group | State College | Pennsylvania | 16801 | United States |
| UPMC Cancer Center-Washington | Washington | Pennsylvania | 15301 | United States |
| Geisinger Wyoming Valley/Henry Cancer Center | Wilkes-Barre | Pennsylvania | 18711 | United States |
| Lankenau Medical Center | Wynnewood | Pennsylvania | 19096 | United States |
| Sanford Cancer Center Oncology Clinic | Sioux Falls | South Dakota | 57104 | United States |
| Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | 57117-5134 | United States |
| Memorial Hospital | Chattanooga | Tennessee | 37404 | United States |
| Pulmonary Medicine Center of Chattanooga-Hixson | Hixson | Tennessee | 37343 | United States |
| Baptist Memorial Hospital and Cancer Center-Memphis | Memphis | Tennessee | 38120 | United States |
| Memorial GYN Plus | Ooltewah | Tennessee | 37363 | United States |
| Saint Joseph Regional Cancer Center | Bryan | Texas | 77802 | United States |
| Parkland Memorial Hospital | Dallas | Texas | 75235 | United States |
| UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | 75390 | United States |
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | 84112 | United States |
| University of Virginia Cancer Center | Charlottesville | Virginia | 22908 | United States |
| Highline Medical Center-Main Campus | Burien | Washington | 98166 | United States |
| Saint Elizabeth Hospital | Enumclaw | Washington | 98022 | United States |
| Saint Francis Hospital | Federal Way | Washington | 98003 | United States |
| Saint Clare Hospital | Lakewood | Washington | 98499 | United States |
| Harrison HealthPartners Hematology and Oncology-Poulsbo | Poulsbo | Washington | 98370 | United States |
| Saint Michael Cancer Center | Silverdale | Washington | 98383 | United States |
| Franciscan Research Center-Northwest Medical Plaza | Tacoma | Washington | 98405 | United States |
| Northwest Medical Specialties PLLC | Tacoma | Washington | 98405 | United States |
| Legacy Salmon Creek Hospital | Vancouver | Washington | 98686 | United States |
| Duluth Clinic Ashland | Ashland | Wisconsin | 54806 | United States |
| Northwest Wisconsin Cancer Center | Ashland | Wisconsin | 54806 | United States |
| Marshfield Medical Center-EC Cancer Center | Eau Claire | Wisconsin | 54701 | United States |
| Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | 54449 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Marshfield Medical Center - Minocqua | Minocqua | Wisconsin | 54548 | United States |
| ProHealth D N Greenwald Center | Mukwonago | Wisconsin | 53149 | United States |
| Cancer Center of Western Wisconsin | New Richmond | Wisconsin | 54017 | United States |
| ProHealth Oconomowoc Memorial Hospital | Oconomowoc | Wisconsin | 53066 | United States |
| Marshfield Medical Center-Rice Lake | Rice Lake | Wisconsin | 54868 | United States |
| Marshfield Medical Center-River Region at Stevens Point | Stevens Point | Wisconsin | 54482 | United States |
| ProHealth Waukesha Memorial Hospital | Waukesha | Wisconsin | 53188 | United States |
| UW Cancer Center at ProHealth Care | Waukesha | Wisconsin | 53188 | United States |
| Marshfield Medical Center - Weston | Weston | Wisconsin | 54476 | United States |
| Billings Clinic-Cody | Cody | Wyoming | 82414 | United States |
| Welch Cancer Center | Sheridan | Wyoming | 82801 | United States |
| FG001 | LDK378 (Ceritinib) | Participants with I1171, L1196 (including L1196M), or V1180 mutations, or no having no ALK-resistance mutations or MET amplifications, can be assigned to receive ceritinib Ceritinib: 450 mg orally once a day with food. Treatment continues until disease progression or unacceptable toxicity. |
| FG002 | Alectinib | Participants with C1156Y, L1196 (including L1196M), or F1174 mutations, or no having no ALK-resistance mutations or MET amplifications, can be assigned to receive Alectinib. Alectinib: 600 mg orally twice daily with food. Treatment continues until disease progression or unacceptable toxicity. |
| FG003 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| FG004 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| FG005 | Crizotinib | Participants with ALK L1198F (alone/ in combination with another ALK mutation) or mesenchymal-to-epithelial transition (MET) amplification can be assigned to receive crizotinib Crizotinib: 250 mg orally twice daily with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| FG006 | Pemetrexed +/- Cisplatin or Carboplatin | Participants with no ALK-resistance mutations or MET amplifications can be assigned to receive pemetrexed, which optionally can be combined with cisplatin or carboplatin. Carboplatin: Carboplatin is optional. Dosing of area under the curve (AUC) = 5 once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed) intravenously, prepared and administered per institution policy. Continues for 4-6 cycles. Cisplatin: Cisplatin is optional. 75 mg/m^2 intravenously once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed), prepared and administered per institution policy. Pemetrexed: Pemetrexed may be given alone or with either cisplatin or carboplatin. Pemetrexed 500 mg/m2 administered intravenously on Day 1 of a 21 day cycle, optionally with cisplatin or carboplatin for 4-6 cycles. Then pemetrexed (as a single agent) continues until progression or significant toxicity. |
| Disease Assessment Population | Eligible participants who started protocol treatment and had post-baseline disease assessment. |
|
| Survival Population | Eligible participants who started protocol treatment and have post-baseline survival status. |
|
| Adverse Event Population | Eligible participants who started protocol treatment and have adverse event data. |
|
| COMPLETED | Participants contributing data to any results are considered to have completed the study. |
|
| NOT COMPLETED |
|
|
Eligible participants assigned to treatment (second step registration)
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lorlatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, compound mutation*, or no mutations, can be assigned to receive lorlatinib. *Compound mutation = two or more resistance mutation excluding those with L1198F or L1189F/MET amplification = L1198F mutation alone or in combination, or no ALK mutation but any MET amplification. Lorlatinib: 100 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| BG001 | LDK378 (Ceritinib) | Participants with I1171, L1196 (including L1196M), or V1180 mutations, or no having no ALK-resistance mutations or MET amplifications, can be assigned to receive ceritinib Ceritinib: 450 mg orally once a day with food. Treatment continues until disease progression or unacceptable toxicity. |
| BG002 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| BG003 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| BG004 | Pemetrexed +/- Cisplatin or Carboplatin | Participants with no ALK-resistance mutations or MET amplifications can be assigned to receive pemetrexed, which optionally can be combined with cisplatin or carboplatin. Carboplatin: Carboplatin is optional. Dosing of area under the curve (AUC) = 5 once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed) intravenously, prepared and administered per institution policy. Continues for 4-6 cycles. Cisplatin: Cisplatin is optional. 75 mg/m^2 intravenously once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed), prepared and administered per institution policy. Pemetrexed: Pemetrexed may be given alone or with either cisplatin or carboplatin. Pemetrexed 500 mg/m2 administered intravenously on Day 1 of a 21 day cycle, optionally with cisplatin or carboplatin for 4-6 cycles. Then pemetrexed (as a single agent) continues until progression or significant toxicity. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Mutation | Count of Participants | Participants |
| ||||||||||||||||
| Has CNS metastases | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria | ORR= number of subjects with best overall response (BOR) of complete or partial response (CR, PR) divided by number of evaluable subjects. BOR= best response recorded from start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.
ORR was to be compared using Fisher's exact test within each ALK inhibitor treatment arm (each mutation vs. no mutation) and also within the subset of subjects with no mutation comparing each experimental arm vs. pemetrexed. Due to early accrual closure (few subjects), only the number of subjects with BOR of CR or PR are provided, by mutation, no statistical testing. Analysis was to occur after each patient was potentially followed ≥ 24 weeks. | Eligible participants who started protocol treatment and had post-baseline disease assessment. Treatment arms with no evaluable participants are not shown. | Posted | Count of Participants | Participants | Baseline to 24 weeks |
|
|
| ||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria | Progression-free survival time is defined as the time from second step registration to the date of the first disease progression / progressive disease (PD), death, or last known follow-up (censored). Progressive disease is defined as a 20% increase of target lesions and/or new lesion(s). Percentage of participants progression-free at a given time (PFS) was to be estimated by the Kaplan-Meier method. Median PFS and PFS at specific time points was to be reported, with 95% confidence intervals, for each mutation (or no mutation)/regimen combination. Due to early accrual closure resulting in few participants, only the number of participants who progressed or died, by mutation, with no statistical testing. | Eligible participants who started protocol treatment and had post-baseline disease assessment. Treatment arms with no evaluable participants are not shown. | Posted | Count of Participants | Participants | Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| ||||||||||||||||||||||||||||||||
| Secondary | Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1 | Duration of overall response (DOR) is defined as the time from the first occurrence of a documented BOR of CR or PR to the first date of recorded disease progression (PD) or death from any cause (whichever occurs first). BOR is the best response recorded from the start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.
Median DOR was to be estimated, with 95% confidence intervals, for each mutation/regimen combination using the Kaplan-Meier method. Due to early accrual closure resulting in few subjects, only the mean and range DOR are provided, by mutation, and no statistical testing was done. | Eligible participants who started protocol treatment and had complete or partial response. Treatment arms with no evaluable participants are not shown. | Posted | Mean | Full Range | months | Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| |||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Survival time is defined as the time from second step registration to the date of death, or last known follow-up (censored). Percentage of participants alive at a given time (OS) was to be estimated by the Kaplan-Meier method. Median OS and OS at specific time points was to be reported, with 95% confidence intervals, for each mutation/regimen combination. Due to early accrual closure resulting in few patients, only the number of participants who died are provided, by mutation, and no statistical testing was done. | Eligible participants who started protocol treatment, with post-baseline survival status. Treatment arms with no evaluable participants are not shown. | Posted | Count of Participants | Participants | Baseline to the date of death or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| ||||||||||||||||||||||||||||||||
| Secondary | Intracranial Objective Response Rate, Per Investigator Assessment Using RECIST v1.1 | Intracranial objective response rate (IORR) is defined as the number of participants with central nervous system (CNS) metastasis complete or partial response (CR, PR) divided by the number of evaluable participants with baseline CNS metastasis and no prior CNS radiation therapy. Participants who required additional treatment (for their non-cranial systemic disease) would be considered as non-responders (if they have not previously had an intracranial response).
IORR was to be estimated for each mutation/regimen combination, with the associated 95% confidence intervals (using Clapper-Pearson method). Due to early accrual closure resulting in few subjects, only the number of subjects with CR or PR are provided, by mutation, with no statistical testing. | No participants with baseline CNS metastasis had evaluable post-baseline CNS metastasis assessment. | Posted | Baseline to 24 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants by Highest Grade Adverse Event Reported | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. | Eligible participants who started protocol treatment, with adverse event data. Treatment arms with no evaluable participants are not shown. | Posted | Count of Participants | Participants | Baseline to the date of last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months. |
| ||||||||||||||||||||||||||||||||
| Other Pre-specified | Agreement of Biopsy Mutation and Circulating Free Deoxyribonucleic Acid (cfDNA) Mutation Results | For each mutation, the agreement of the biopsy result (present, absent, unavailable) and the cfDNA result (present, absent, unavailable) would be assessed. Agreement of cfDNA and biopsy results will be considered separately for MET amplification and for the gene mutations. This outcome measure was to be contingent upon FDA approval of the outcome measure analysis plan, which was not pursued due to the early accrual closure. | No assay data for analysis was received. | Posted | Baseline |
|
Baseline to the date of last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.
Note, treatment arms are reported by mutation / no mutation.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lorlatinib (Mutations) | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or compound mutation*. *Compound mutation = two or more resistance mutation excluding those with L1198F or L1189F/MET amplification = L1198F mutation alone or in combination, or no ALK mutation but any MET amplification. Lorlatinib: 100 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG001 | Lorlatinib (no Mutations) | Participants with no ALK-resistance mutations or MET amplifications. Lorlatinib: 100 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. | 0 | 2 | 2 | 2 | 2 | 2 |
| EG002 | LDK378 (Ceritinib) | Participants with I1171, L1196 (including L1196M), or V1180 mutations. Ceritinib: 450 mg orally once a day with food. Treatment continues until disease progression or unacceptable toxicity. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG003 | Brigatinib (Mutations) | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG004 | Brigatinib (no Mutations) | Participants with no ALK-resistance mutations or MET amplifications. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. | 1 | 1 | 1 | 1 | 1 | 1 |
| EG005 | Ensartinib | Participants with no ALK-resistance mutations or MET amplifications. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. | 2 | 3 | 1 | 3 | 2 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericardial effusion | Cardiac disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Infections and infestations - Other | Infections and infestations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (5.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Cardiac disorders - Other | Cardiac disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Blurred vision | Eye disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Gastrointestinal disorders - Other | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Edema limbs | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Flu like symptoms | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Generalized edema | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Localized edema | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hepatobiliary disorders - Other | Hepatobiliary disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Infections and infestations - Other | Infections and infestations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Papulopustular rash | Infections and infestations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | CTCAE (5.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Cholesterol high | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Lipase increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Serum amylase increased | Investigations | CTCAE (5.0) | Non-systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Muscle cramp | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Memory impairment | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Nervous system disorders - Other | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Paresthesia | Nervous system disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hallucinations | Psychiatric disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Sleep apnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Bullous dermatitis | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Surgical and medical procedures - Other | Surgical and medical procedures | CTCAE (5.0) | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (5.0) | Non-systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (5.0) | Non-systematic Assessment |
|
This study stopped accrual early due to unmet targeted accrual goals with 10 subjects randomized out of 660 planned. Study assessments and data collection continued only for those participants still receiving study treatment and ceased at treatment completion.
Must obtain prior approval from the sponsor. In addition, PI's are required to abide by Collaborator's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wendy Seiferheld | NRG Oncology | 215-574-3208 | seiferheldw@nrgoncology.org |
| Jun 2, 2023 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: Treatment with Alectinib | Nov 14, 2024 | Feb 3, 2025 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Treatment with Brigatinib | Nov 14, 2024 | Feb 3, 2025 | ICF_002.pdf |
| ICF | No | No | Yes | Informed Consent Form: Treatment with LDK378 (Ceritinib) | Nov 14, 2024 | Feb 3, 2025 | ICF_003.pdf |
Not provided
| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C582670 | alectinib |
| C000598580 | brigatinib |
| D016190 | Carboplatin |
| C586847 | ceritinib |
| D002945 | Cisplatin |
| C044245 | 1,2-diaminocyclohexaneplatinum II citrate |
| D010984 | Platinum |
| D000077547 | Crizotinib |
| C000629294 | ensartinib |
| C000590786 | lorlatinib |
| D000068437 | Pemetrexed |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D028561 | Transition Elements |
| D008670 | Metals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000631 | Aminopyridines |
| D011725 | Pyridines |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
Not provided
Not provided
| 50-59 years |
|
| 60-69 years |
|
| >= 70 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| No ALK-resistance mutation / MET amplification |
|
|
| Mutation = None: BOR of CR or PR |
|
|
| OG001 | LDK378 (Ceritinib) | Participants with I1171, L1196 (including L1196M), or V1180 mutations, or no having no ALK-resistance mutations or MET amplifications, can be assigned to receive ceritinib. Ceritinib: 450 mg orally once a day with food. Treatment continues until disease progression or unacceptable toxicity. |
| OG002 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| OG003 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
|
|
| OG001 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
|
|
Participants with I1171, L1196 (including L1196M), or V1180 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive ceritinib
Ceritinib: 450 mg orally once a day with food. Treatment continues until disease progression or unacceptable toxicity.
| OG002 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| OG003 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
|
|
|
| OG002 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| OG003 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
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| OG002 | Alectinib | Participants with C1156Y, L1196 (including L1196M), or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive Alectinib. Alectinib: 600 mg orally twice daily with food. Treatment continues until disease progression or unacceptable toxicity. |
| OG003 | Brigatinib | Participants with G1202 (including G1202del and G1202R), C1156Y, I1171, L1196 (including L1196M), V1180, or F1174 mutations, or having no ALK-resistance mutations or MET amplifications, can be assigned to receive brigatinib. Brigatinib: 90 mg orally once a day (with or without food) for the first 7 days; if tolerated, with no respiratory symptoms, increase the dose to 180 mg once daily. Treatment continues until disease progression or unacceptable toxicity. |
| OG004 | Ensartinib | Participants with L1196 (including L1196M) mutations or having no ALK-resistance mutations or MET amplifications can be assigned to receive ensartinib. Ensartinib: 225 mg orally once a day with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| OG005 | Crizotinib | Participants with ALK L1198F (alone/ in combination with another ALK mutation) or mesenchymal-to-epithelial transition (MET) amplification can be assigned to receive crizotinib Crizotinib: 250 mg orally twice daily with or without food. Treatment continues until disease progression or unacceptable toxicity. |
| OG006 | Pemetrexed +/- Cisplatin or Carboplatin | Participants with no ALK-resistance mutations or MET amplifications can be assigned to receive pemetrexed, which optionally can be combined with cisplatin or carboplatin. Carboplatin: Carboplatin is optional. Dosing of area under the curve (AUC) = 5 once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed) intravenously, prepared and administered per institution policy. Continues for 4-6 cycles. Cisplatin: Cisplatin is optional. 75 mg/m^2 intravenously once every 3 weeks (on Day 1 of a 21 day cycle with pemetrexed), prepared and administered per institution policy. Pemetrexed: Pemetrexed may be given alone or with either cisplatin or carboplatin. Pemetrexed 500 mg/m2 administered intravenously on Day 1 of a 21 day cycle, optionally with cisplatin or carboplatin for 4-6 cycles. Then pemetrexed (as a single agent) continues until progression or significant toxicity. |
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