MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

NCT02444884 | Completed Phase 1 DMC

• 1 other identifier: ADVL0812
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors

Conditions

Unspecified Childhood Solid Tumor, Excluding CNS; Neuroblastoma

Outcome Measures

Primary Outcomes (4)

• Determine maximum tolerated dose and RP2D administered once daily on Days 1-7

  Up to 21 days (1st cycle) of protocol therapy

• Determine maximum tolerated dose and RP2D administered po BID on Days 1-7

  Up to 21 days (1st cycle) of protocol therapy

• Adverse events as assessed by (CTCAE) version 4.0

  DLT will be defined as possibly, probably or definitely attributable to MLN8237. The DLT observation period for the purposes of dose-escalation will be the first cycle of therapy

  Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]

• PK Profile: MLN8237 concentrations in plasma samples

  single-dose AUC, trough estimation, t½ of accumulation

  30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1

Study Arms (3)

Stratum A1

EXPERIMENTAL

Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7

Drug: MLN8237

Stratum A2

EXPERIMENTAL

MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7

Drug: MLN8237

Stratum B

EXPERIMENTAL

Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7

Drug: MLN8237

Interventions

MLN8237 DRUG

Also known as: Alisertib

Stratum A1; Stratum A2; Stratum B

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetaprotein or beta-HCG.
• Performance Level: Karnofsky \>/= 50% for patients \> 16 years of age and Lansky
• \>/= 50 for patients \</=16 years of age
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Adequate Bone Marrow Function Defined as:
• a. For patients with solid tumors:
• Peripheral absolute neutrophil count (ANC) \>/= 1000/microLiter
• Platelet count \>/= 100,000/microLiter (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
• Hemoglobin \>/= 8.0 g/dL (may receive RBC transfusions)
• Creatinine clearance or radioisotope GFR \>/= 70ml/min/1.73 m2
• Bilirubin (sum of conjugated + unconjugated) \</= 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) \</= 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L.
• Serum albumin \>/= 2 g/dL.

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study
• Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment.
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible.
• Patients who are currently receiving another investigational drug are not eligible.
• Patients who are currently receiving other anticancer agents, digoxin, cyclosporine, tacrolimus or sirolimus, use of daily benzodiazepines are not eligible
• Patients who have an uncontrolled infection are not eligible.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Related Publications (1)

• Zhou X, Mould DR, Yuan Y, Fox E, Greengard E, Faller DV, Venkatakrishnan K. Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies. J Clin Pharmacol. 2022 Feb;62(2):206-219. doi: 10.1002/jcph.1958. Epub 2022 Jan 15.

  PMID: 34435684 DERIVED

MeSH Terms

Conditions

Neuroblastoma

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 15, 2015
• Study Start: September 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 9, 2016

Record last verified: 2016-02