Clinical trial · Interventional
Study of MLN8237 in Combination With Irinotecan and Temozolomide
Phase I/II Study of MLN8237 in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma
NCT01601535CI-TRIAL-00039828completedPhase 1 / Phase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Neuroblastoma | Neuroblastoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Irinotecan | Drug | Irinotecan | ALIAS |
| MLN8237 | Drug | Alisertib | ALIAS |
| Temozolomide | Drug | Temozolomide | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment
- description
- 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.
- interventionNames
- Drug: MLN8237
- Drug: Irinotecan
- Drug: Temozolomide
Primary outcomes (9)
- measure
- Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma
- timeFrame
- 21 days, from study day 1
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 12 Months
- Maximum age
- 30 Years
Show eligibility criteria text
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: * Patients who have received prior MLN8237 are excluded from all phases of the study. Patients previously treated with irinotecan and/or temozolomide will be eligible if they have not had documented progressive disease during treatment with a regimen containing these agents. * They have other medical problems that could get much worse if they had this treatment. * They are on dialysis for bad kidney function. * They are pregnant or breast feeding. * They have active infections such as hepatitis or fungal infections. * They have an allergy to treatment with cefixime and cefpodixime. * They have brain metastasis at study entry, or have received cranial spinal radiation. * They have had an allogeneic stem cell transplant (received stem cell from someone else). * They can't cooperate with the special precautions that are needed for this trial.
References
Publications (1)
- DERIVEDDuBois 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. PMID 30093449