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The goal of the first part of this clinical trial (Phase I portion) is to study the side effects, drug breakdown (pharmacokinetics), and dosing of the drug MLN8237 when added to standard chemotherapy drugs, irinotecan and temozolomide.
The goal of the second part of this clinical trial (Phase II portion) is to learn how many children and young adults show improvements in their neuroblastoma when treated with the combination of MLN8237, irinotecan, and temozolomide.
The Aurora A kinase has been shown to play an important role in neuroblastoma growth. Inhibition of Aurora A kinase activity attenuates the growth of neuroblastoma cells. MLN8237 is a selective small molecule inhibitor of Aurora A kinase that has completed pediatric single-agent phase I testing, as well as stage 1 phase 2 testing in patients with Neuroblastoma. MLN8237 showed activity against the NCI-sponsored Pediatric Preclinical Testing Program neuroblastoma in vivo panel that exceeded the activity level observed with chemotherapy agents routinely used in the treatment of neuroblastoma. Additional in vitro and in vivo studies have shown that Aurora A kinase inhibitors result in enhanced cytotoxicity when used in combination with chemotherapy. Irinotecan and temozolomide is a commonly used salvage regimen for patients with relapsed or refractory neuroblastoma. This combination has a modest objective response rate (16%) and is well-tolerated, suggesting that it will provide a useful platform for the study of novel compounds in combination with chemotherapy. Preclinical studies demonstrate marked enhancement of anti-neuroblastoma activity with the addition of MLN8237 to irinotecan and temozolomide. This study therefore evaluates the tolerability and activity of MLN8237 in combination with irinotecan and temozolomide in children with refractory or relapsed neuroblastoma. Patients receive irinotecan (50 mg/m2/dose IV) and temozolomide (100 mg/m2/dose orally) once daily for 5 days along with MLN8237 orally once daily for 7 days. The doses of irinotecan and temozolomide will be fixed and the dose of MLN8237 will be dose-escalated. In the phase I portion of the study, the primary aims are to determine the recommended phase II doses of this combination, describe the toxicity of this combination, and characterize the pharmacokinetic profile of MLN8237 and irinotecan when used in combination. In the phase II portion of the study, the primary aim is to determine the objective response rate of this combination in patients with relapsed or refractory neuroblastoma. With Amendment 5, the tolerability and pharmacokinetics of an MLN8237 oral solution will be evaluated. Optional correlative studies will evaluate UGT1A1 polymorphisms as predictors of toxicity and archival tumor tissue Aurora A expression as a predictor of response with this combination.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Every course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7. Irinotecan will be administered intravenously during each course on study day 1 through day 5. Temozolomide will be administered orally during each course on study day 1 through day 5. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MLN8237 | Drug | Every course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma | The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy. | 21 days, from study day 1 |
| Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose | The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy. | 21 days, from study day 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax |
| Measure | Description | Time Frame |
|---|---|---|
| Aurora A Expression | To explore whether MYCN status and markers of expression of Aurora A in archival tumor tissue are associated with the antitumor activity of the combination of MLN8237, irinotecan, and temozolomide | From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years). |
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Criteria that need to be met to participate in this study:
Patients must be > 12 months and < 30 years of age when registered on study.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment. All patients must have at least ONE site of evaluable disease.
o Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
MLN8237 must be swallowed as whole tablets. Therefore, patients must be able to swallow pills to be eligible for study. One tablet is the size of small breath mint, or baby aspirin. Due to the size of MLN8237 tablets, patients must have a body surface area of at least 0.38 m2 to be eligible for study. A body surface area is a combination of a patient's height and weight. An example of a child with a BSA of 0.45 is a child that is 25 inches tall and weighs 25 pounds.You can use the link below to calculate your child's body surface area and determine if they are too small for this trial.
Patients cannot participate in the study if:
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| Name | Affiliation | Role |
|---|---|---|
| Steven DuBois, MD | Dana-Farber Cancer Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027-0700 | United States | ||
| Lucile Packard Children's Hospital at Stanford University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30093449 | Derived | DuBois SG, Mosse YP, Fox E, Kudgus RA, Reid JM, McGovern R, Groshen S, Bagatell R, Maris JM, Twist CJ, Goldsmith K, Granger MM, Weiss B, Park JR, Macy ME, Cohn SL, Yanik G, Wagner LM, Hawkins R, Courtier J, Lai H, Goodarzian F, Shimada H, Boucher N, Czarnecki S, Luo C, Tsao-Wei D, Matthay KK, Marachelian A. Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res. 2018 Dec 15;24(24):6142-6149. doi: 10.1158/1078-0432.CCR-18-1381. Epub 2018 Aug 9. |
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| ID | Title | Description |
|---|---|---|
| FG000 | DL 1 | alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional |
| FG001 | DL 1B |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 10, 2018 |
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| Irinotecan | Drug | Irinotecan will be administered intravenously during each course on study day 1 through day 5. |
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| Temozolomide | Drug | Temozolomide will be administered orally during each course on study day 1 through day 5. |
|
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Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. |
| 1st week of cycle 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | 1st week of cycle 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | 1st week of cycle 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | 1st week of cycle 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | 1st week of cycle 1 |
| Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | 1st week of cycle 1 |
| Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD | Response was graded according to version 1.2 of the NANT response criteria that classifies patients as having one of the following overall response categories based upon underlying response at soft tissue sites, MIBG positive sites, and bone marrow disease: complete response (CR); CR with minimal residual disease (CR-MRD); partial response (PR); minor response (MR); stable disease (SD); and progressive disease (PD). These criteria utilize RECIST criteria for measurable tumors, Curie score for MIBG scan response, and bone marrow (BM) morphology. BM response was graded as CR (required two time points to confirm), CR unconfirmed (one time point only), CR-MRD (bone marrow involvement < 5% at study entry with negative follow-up biopsies), SD, or PD. Patients with at least SD or better underwent central review of MIBG scans, CT scans, and bone marrow pathology slides. Overall responses of CR, CR-MRD, or PR were considered objective responses. | Cycles repeated every 21 days for up to 34 cycles. |
| UGT1A1 Genotype |
To explore whether UGT1A1 genotype is associated with toxicity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide |
| Day 7 of cycle 1 |
| AURKA Genotype | To explore whether AURKA genotype is associated with antitumor activity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide. | Day 7 of cycle 1 |
| One Year Progression Free Survival Rate | To determine the progression free survival rates for patients with relapsed or refractory neuroblastoma treated with MLN8237, irinotecan, and temozolomide at the identified MTD | 1 Years after completion of study |
| Palo Alto |
| California |
| 94304 |
| United States |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94115 | United States |
| Children Hospital of Colorado | Aurora | Colorado | 80045 | United States |
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| University of Chicago Comer Children's Hospital | Chicago | Illinois | 60637 | United States |
| Childrens Hospital Boston, Dana-Farber Cancer Institute. | Boston | Massachusetts | 02115 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229-3039 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104-4318 | United States |
| Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | 76104 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| FG002 | DL 2B | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| FG003 | DL 3B | alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| FG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| FG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| COMPLETED |
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| NOT COMPLETED |
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| Phase 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | DL 1 | alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional |
| BG001 | DL 1B | alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| BG002 | DL 2B | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| BG003 | DL 3B | alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| BG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| BG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Prior Irinotecan | Count of Participants | Participants |
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| Prior Temozolomide | Count of Participants | Participants |
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| 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 | ||||||||||||||||||||
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| Primary | Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma | The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy. | Posted | Number | mg/m^2 | 21 days, from study day 1 |
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| Primary | Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose | The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy. | Posted | Number | DLTs | 21 days, from study day 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | µM | 1st week of cycle 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | hour | 1st week of cycle 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | µM•hour | 1st week of cycle 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | ng/mL | 1st week of cycle 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | h·ng/mL | 1st week of cycle 1 |
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| Primary | Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance | Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan. | Posted | Median | Full Range | L/h | 1st week of cycle 1 |
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| Primary | Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD | Response was graded according to version 1.2 of the NANT response criteria that classifies patients as having one of the following overall response categories based upon underlying response at soft tissue sites, MIBG positive sites, and bone marrow disease: complete response (CR); CR with minimal residual disease (CR-MRD); partial response (PR); minor response (MR); stable disease (SD); and progressive disease (PD). These criteria utilize RECIST criteria for measurable tumors, Curie score for MIBG scan response, and bone marrow (BM) morphology. BM response was graded as CR (required two time points to confirm), CR unconfirmed (one time point only), CR-MRD (bone marrow involvement < 5% at study entry with negative follow-up biopsies), SD, or PD. Patients with at least SD or better underwent central review of MIBG scans, CT scans, and bone marrow pathology slides. Overall responses of CR, CR-MRD, or PR were considered objective responses. | The analysis was performed on 19 phase II patients, with 1 inevaluable patient excluded. | Posted | Count of Participants | Participants | Cycles repeated every 21 days for up to 34 cycles. |
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| Secondary | Aurora A Expression | To explore whether MYCN status and markers of expression of Aurora A in archival tumor tissue are associated with the antitumor activity of the combination of MLN8237, irinotecan, and temozolomide | Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts. | Posted | Number | participants | From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years). |
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| Secondary | UGT1A1 Genotype | To explore whether UGT1A1 genotype is associated with toxicity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide | Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts. | Posted | Number | participants | Day 7 of cycle 1 |
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| Secondary | AURKA Genotype | To explore whether AURKA genotype is associated with antitumor activity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide. | Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts. | Posted | Number | participants | Day 7 of cycle 1 |
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| Secondary | One Year Progression Free Survival Rate | To determine the progression free survival rates for patients with relapsed or refractory neuroblastoma treated with MLN8237, irinotecan, and temozolomide at the identified MTD | The analysis was performed in phase II patients. | Posted | Count of Participants | Participants | 1 Years after completion of study |
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From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DL 1 | alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional | 0 | 6 | 3 | 6 | 6 | 6 |
| EG001 | DL 1B | alisertib tablets (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required | 0 | 6 | 3 | 6 | 6 | 6 |
| EG002 | DL 2B | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required | 0 | 6 | 3 | 6 | 6 | 6 |
| EG003 | DL 3B | alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required | 0 | 4 | 2 | 4 | 4 | 4 |
| EG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required | 0 | 20 | 1 | 20 | 20 | 20 |
| EG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required | 0 | 12 | 2 | 12 | 12 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
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| Mucositis oral | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
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| Catheter related infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment |
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| Infections and infestations - Other, specify | Infections and infestations | CTCAE v4.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE v4.0 | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Movements involuntary | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hemolysis | Blood and lymphatic system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Palpitations | Cardiac disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Sinus tachycardia | Cardiac disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Ear pain | Ear and labyrinth disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypothyroidism | Endocrine disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Blurred vision | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Conjunctivitis | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dry eye | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Eye disorders - Other, specify | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Eye pain | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Photophobia | Eye disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Abdominal distension | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Anal pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Colitis | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Constipation | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dental caries | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dry mouth | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Enterocolitis | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Flatulence | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Nausea | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Oral dysesthesia | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Oral hemorrhage | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Oral pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Rectal pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Stomach pain | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Toothache | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Vomiting | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Chills | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Edema face | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Edema trunk | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Facial pain | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Fatigue | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Fever | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| General disorders and administration site conditions - Other, specify | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Infusion related reaction | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Infusion site extravasation | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Irritability | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Malaise | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Non-cardiac chest pain | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Pain | General disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Conjunctivitis infective | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Enterocolitis infectious | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Lung infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Mucosal infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Otitis externa | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Otitis media | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Rhinitis infective | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Sepsis | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Skin infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Upper respiratory infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Urinary tract infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Vaginal infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Burn | Injury, poisoning and procedural complications | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Fall | Injury, poisoning and procedural complications | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Vascular access complication | Injury, poisoning and procedural complications | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Alanine aminotransferase increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Alkaline phosphatase increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Aspartate aminotransferase increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Blood bilirubin increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Creatinine increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Electrocardiogram QT corrected interval prolonged | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| GGT increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hemoglobin increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Investigations - Other, specify | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Lymphocyte count decreased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Lymphocyte count increased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Neutrophil count decreased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Platelet count decreased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Weight gain | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Weight loss | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| White blood cell decreased | Investigations | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Acidosis | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Metabolism and nutrition disorders - Other, specify | Metabolism and nutrition disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Depressed level of consciousness | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dizziness | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dysgeusia | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Headache | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Nervous system disorders - Other, specify | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Paresthesia | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Peripheral motor neuropathy | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Presyncope | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Somnolence | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Syncope | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Tremor | Nervous system disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Agitation | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Anxiety | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Depression | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hallucinations | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Insomnia | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Psychiatric disorders - Other, specify | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Restlessness | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hematuria | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Proteinuria | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Urinary retention | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Urinary tract pain | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Urine discoloration | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Penile pain | Reproductive system and breast disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Apnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Bullous dermatitis | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Urticaria | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Surgical and medical procedures - Other, specify | Surgical and medical procedures | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Flushing | Vascular disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hematoma | Vascular disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypertension | Vascular disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
| Hypotension | Vascular disorders | CTCAE v4.0 | Systematic Assessment | As requested, we are reporting all toxicities of all grades, whether or not they are related to the regimen or known to be related to non-treatment causes. |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| NANT Medical Director | New Approaches to Neuroblastoma Therapy | 323-361-5687 | nantops@chla.usc.edu |
| May 30, 2019 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C550258 | MLN 8237 |
| D000077146 | Irinotecan |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Withdrawal by Subject |
|
| Progressive Disease |
|
| Started Another Treatment |
|
| Male |
|
| Not Hispanic Black or African American |
|
| Not Hispanic White |
|
| Not Hispanic Other |
|
| Not Hispanic Unknown |
|
| No |
|
| No |
|
| OG002 | DL 2B | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG003 | DL 3B | alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
|
alisertib tablets (80 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG004 | Ph 2 | alisertib tablets (60 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
| OG005 | Oral Solution | alisertib oral solution (45 mg/m^2/dose x 7 days), irinotecan (50 mg/m^2/dose IV x 5 days), temozolomide (100 mg/m^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required |
|
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