MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

February 5, 2016 updated by: Children's Oncology Group

A Phase I/II Study of MLN8237, an Oral Selective Small Molecule Inhibitor of Aurora A Kinase, in Children With Relapsed/Refractory Solid Tumors

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

1.1 Primary Aims 1.1.1 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally once daily for 7 days every 21 days to children with refractory solid tumors. 1.1.2 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally twice daily for 7 days every 21 days to children with refractory solid tumors. 1.1.3 To define and describe the toxicities of MLN8237 administered on this schedule.

1.1.4 To characterize the pharmacokinetics of MLN8237 in children with refractory cancer.

1.2 Secondary Aims 1.2.1 To preliminarily define the antitumor activity of MLN8237 within the confines of a Phase I study. 1.2.2 To obtain initial Phase II efficacy data on the anti-tumor activity of MLN8237 in children with relapsed-refractory neuroblastoma using the once daily dosing schedule. 1.2.3 To explore the relationship between polymorphic variations in the UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237.

1.2.4 To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis. 1.2.5 To preliminarily examine the relationsh

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stratum A1
Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7
Drug: MLN8237
Other Names:
  • Alisertib
Experimental: Stratum A2
MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7
Drug: MLN8237
Other Names:
  • Alisertib
Experimental: Stratum B
Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7
Drug: MLN8237
Other Names:
  • Alisertib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
Time Frame: Up to 21 days (1st cycle) of protocol therapy
Up to 21 days (1st cycle) of protocol therapy
Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
Time Frame: Up to 21 days (1st cycle) of protocol therapy
Up to 21 days (1st cycle) of protocol therapy
Adverse events as assessed by (CTCAE) version 4.0
Time Frame: Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
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
Time Frame: 30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

May 7, 2015

First Submitted That Met QC Criteria

May 12, 2015

First Posted (Estimate)

May 15, 2015

Study Record Updates

Last Update Posted (Estimate)

February 9, 2016

Last Update Submitted That Met QC Criteria

February 5, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADVL0812

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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