Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes.
PRIMARY OBJECTIVES:
I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies.
II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
SECONDARY OBJECTIVES:
I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent development of targeted therapies against genotype-defined subpopulations in the adjuvant and recurrent settings.
II. To cross-validate local genotyping assays for EGFR and ALK and PD-L1 immunohistochemistry (IHC) with a central reference standard, when available.
EXPLORATORY/OTHER OBJECTIVES:
I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for potentially eligible patients.
III. To study the clinical significance of circulating tumor DNA within the plasma cell-free DNA (cfDNA) from early stage lung cancer patients.
IV. To perform proteomic analyses on lung cancer specimens obtained at the time of resection (to identify prognostic biomarkers).
OUTLINE:
STEP 1 (SCREENING): Patients undergo collection of blood and tissue samples for EGFR, ALK, and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 4 treatment subprotocols.
A081105: Patients are randomized to 1 of 4 treatment arms.
ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
E4512: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive crizotinib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM B: Patients undergo observation.
EA5142: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET)/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an echocardiography (ECHO) as clinically indicated on study.
ARM II: Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.
A081801: Patients are randomized to 1 of 3 arms.
ARM A:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then undergo observation.
ARM B:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
ARM C:
INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
*ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle.
DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle.
DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.
DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 of each cycle.
After completion of study, patients that are not enrolled on either A081105, E4512, EA5142, or A081801 are followed up every 6 months for 5 years.
Inclusion Criteria:
PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
For pre-surgical patients
For post-surgical patients
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Age ≥ 18 years
No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
No patients known to be pregnant or lactating
Patients who have had local genotyping are eligible, regardless of the local result
No patients with recurrence of lung cancer after prior resection
Note: Post-surgical patients should proceed to registration immediately following preregistration
PATIENT REGISTRATION ELIGIBILITY CRITERIA:
Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
Completely resected NSCLC with negative margins (R0); cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology
Pathologic stage IIIA, IIA or IIB, or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows:
Squamous patients:
Non-squamous patients:
Jonesboro, Arkansas 72401, United States
Burbank, California 91505, United States
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Sacramento, California 95817, United States
West Haven, Connecticut 06516, United States
Washington D.C., District of Columbia 20002, United States
Deerfield Beach, Florida 33442, United States
Miami, Florida 33136, United States
Highland Park, Illinois 60035, United States
Council Bluffs, Iowa 51503, United States
Louisville, Kentucky 40202, United States
Covington, Louisiana 70433, United States
Slidell, Louisiana 70458, United States
Slidell, Louisiana 70458, United States
Baltimore, Maryland 21237, United States
Brighton, Massachusetts 02135, United States
Milford, Massachusetts 01757, United States
South Weymouth, Massachusetts 02190, United States
Winchester, Massachusetts 01890, United States
Brighton, Michigan 48114, United States
Brownstown, Michigan 48183, United States
Chelsea, Michigan 48118, United States
East China Township, Michigan 48054, United States
Grand Rapids, Michigan 49503, United States
Grand Rapids, Michigan 49503, United States
Norton Shores, Michigan 49444, United States
Saint Joseph, Michigan 49085, United States
Saint Joseph, Michigan 49085, United States
West Branch, Michigan 48661, United States
Ypsilanti, Michigan 48197, United States
Columbus, Mississippi 39705, United States
New Albany, Mississippi 38652, United States
North Kansas City, Missouri 64116, United States
Las Vegas, Nevada 89109, United States
Las Vegas, Nevada 89113, United States
Las Vegas, Nevada 89149, United States
Lebanon, New Hampshire 03756, United States
New Brunswick, New Jersey 08903, United States
Brooklyn, New York 11209, United States
East Syracuse, New York 13057, United States
Mount Kisco, New York 10549-3417, United States
New York, New York 10032, United States
Statesville, North Carolina 28677, United States
Washington, North Carolina 27889, United States
Westerville, Ohio 43082, United States
Cranberry Township, Pennsylvania 16066, United States
East Norriton, Pennsylvania 19401, United States
Harrisburg, Pennsylvania 17109, United States
Mechanicsburg, Pennsylvania 17050, United States
Mount Pleasant, Pennsylvania 15666, United States
N. Huntingdon, Pennsylvania 15642, United States
Collierville, Tennessee 38017, United States
Johnson City, Tennessee 37604, United States
Houston, Texas 77030, United States
American Fork, Utah 84003, United States
Berlin Corners, Vermont 05602, United States
White River Junction, Vermont 05009, United States
Silverdale, Washington 98383, United States
Spokane, Washington 99204, United States
Spokane, Washington 99218, United States
Spokane Valley, Washington 99216, United States
Yakima, Washington 98902, United States
Appleton, Wisconsin 54915, United States
Brookfield, Wisconsin 53045, United States
Franklin, Wisconsin 53132, United States
Johnson Creek, Wisconsin 53038, United States
Madison, Wisconsin 53718, United States
Madison, Wisconsin 53792, United States
Mequon, Wisconsin 53097, United States
Milwaukee, Wisconsin 53210, United States
Stevens Point, Wisconsin 54482, United States
Sturgeon Bay, Wisconsin 54235-1495, United States
Summit, Wisconsin 53066, United States
Wauwatosa, Wisconsin 53226, United States