Phase 2
Completed N=22
Study of MLN8237 in Combination With Irinotecan and Temozolomide
Source: ClinicalTrials.gov NCT01601535 ↗Enrolled (actual)
22
Serious AEs
25.9%
Results posted
Jul 2019
Primary outcomePrimary: Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma — 60 mg/m^2
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
60 | — |
| PRIMARY Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose |
2; 0; 1; 2 | — |
| 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 |
0.48; 0.35; 0.3; 0.73; 0.47; 0.37 | — |
| 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 |
2.04; 1.74; 2.5; 2.52; 2; 7.20 | — |
| PRIMARY Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC |
28.15; 21; 30.71; 47.73; 58.15 | — |
| 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 |
722; 703; 1,238; 784; 881; 732 | — |
| 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 |
3,702; 2,680; 3,957; 2,615; 3,533; 3,121 | — |
| PRIMARY Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance |
14.0; 15.7; 10.4; 16.0; 12.6; 10.3 | — |
| PRIMARY Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD |
0; 0; 4; 2; 8; 5 | — |
| SECONDARY Aurora A Expression |
1; 14; 9; 24; 2; 4 | 0.14 |
| SECONDARY UGT1A1 Genotype |
2; 15; 8; 9; 3; 14 | 0.094 |
| SECONDARY AURKA Genotype |
3; 9; 0; 1; 5; 22 | 0.90 |
| SECONDARY One Year Progression Free Survival Rate |
4 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT01601535). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.