Clinical trial · Interventional

MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

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

NCT02444884CI-TRIAL-00020845completedPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions (2)

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
Unspecified Childhood Solid Tumor, Excluding CNS	Childhood Solid Neoplasm	ALIAS	0.85

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
MLN8237	Drug	Alisertib	ALIAS

Design

Arms and outcomes

Arms (3)

type
EXPERIMENTAL
label
Stratum A1
description
Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7
interventionNames
1. Drug: MLN8237
type
EXPERIMENTAL
label
Stratum A2
description
MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7
interventionNames
1. Drug: MLN8237
type
EXPERIMENTAL
label
Stratum B
description
Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 12 Months
Maximum age: 21 Years

Show eligibility criteria text

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.

References

Publications (1)

DERIVEDZhou 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