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MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

Primary Purpose

Unspecified Childhood Solid Tumor, Excluding CNS, Neuroblastoma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MLN8237
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unspecified Childhood Solid Tumor, Excluding CNS

Eligibility Criteria

12 Months - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Stratum A1

    Stratum A2

    Stratum B

    Arm Description

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

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

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

    Outcomes

    Primary Outcome Measures

    Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
    Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
    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
    PK Profile: MLN8237 concentrations in plasma samples
    single-dose AUC, trough estimation, t½ of accumulation

    Secondary Outcome Measures

    Full Information

    First Posted
    May 7, 2015
    Last Updated
    February 5, 2016
    Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02444884
    Brief Title
    MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors
    Official Title
    A Phase I/II Study of MLN8237, an Oral Selective Small Molecule Inhibitor of Aurora A Kinase, in Children With Relapsed/Refractory Solid Tumors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2016
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2008 (undefined)
    Primary Completion Date
    December 2011 (Actual)
    Study Completion Date
    December 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Unspecified Childhood Solid Tumor, Excluding CNS, Neuroblastoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    54 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Stratum A1
    Arm Type
    Experimental
    Arm Description
    Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7
    Arm Title
    Stratum A2
    Arm Type
    Experimental
    Arm Description
    MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7
    Arm Title
    Stratum B
    Arm Type
    Experimental
    Arm Description
    Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7
    Intervention Type
    Drug
    Intervention Name(s)
    MLN8237
    Other Intervention Name(s)
    Alisertib
    Primary Outcome Measure Information:
    Title
    Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
    Time Frame
    Up to 21 days (1st cycle) of protocol therapy
    Title
    Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
    Time Frame
    Up to 21 days (1st cycle) of protocol therapy
    Title
    Adverse events as assessed by (CTCAE) version 4.0
    Description
    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
    Time Frame
    Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
    Title
    PK Profile: MLN8237 concentrations in plasma samples
    Description
    single-dose AUC, trough estimation, t½ of accumulation
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    12 Months
    Maximum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    34435684
    Citation
    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.
    Results Reference
    derived

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    MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

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