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Trials / Completed

CompletedNCT01606878

Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

A Phase 1 Study of Crizotinib in Combination With Conventional Chemotherapy for Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
46 (actual)
Sponsor
Children's Oncology Group · Network
Sex
All
Age
13 Months – 21 Years
Healthy volunteers
Not accepted

Summary

This phase I trial studies the side effects and the best dose of crizotinib when given together with combination chemotherapy in treating younger patients with solid tumors or anaplastic large cell lymphoma that has returned or does not respond to treatment. Crizotinib may stop the growth of tumor or cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, topotecan hydrochloride, dexrazoxane hydrochloride, doxorubicin hydrochloride, and vincristine sulfate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving crizotinib together with combination chemotherapy may be a better treatment for patients with solid tumors or anaplastic large cell lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of crizotinib administered orally twice daily in combination with topotecan (topotecan hydrochloride) and cyclophosphamide in children with refractory/relapsed solid tumors or anaplastic large cell lymphoma (ALCL). II. To define and describe the toxicities of crizotinib in combination with topotecan and cyclophosphamide administered on this schedule. III. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of crizotinib administered orally twice daily in combination with vincristine (vincristine sulfate) and doxorubicin (doxorubicin hydrochloride)/dexrazoxane (dexrazoxane hydrochloride) in children with refractory/relapsed solid tumors or ALCL. IV. To define and describe the toxicities of crizotinib in combination with vincristine and doxorubicin/dexrazoxane administered on this schedule. V. To characterize the pharmacokinetics of crizotinib in children with relapsed/refractory cancer when combined with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane within the confines of a Phase 1 study. II. To preliminarily examine the relationship between anaplastic lymphoma kinase (ALK) status in patients with neuroblastoma or ALCL and response to crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane. III. To preliminarily examine the relationship between minimal residual disease (MRD) status and clinical response to crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane in patients with ALCL. IV. To use a questionnaire to gather preliminary information on the palatability of the oral solution formulation of crizotinib. V. To examine ALK and MET proto-oncogene (c-Met) expression, copy number and mutations status in archival tumor tissue from solid tumor and ALCL patients. VI. To use a questionnaire to gather information on the acceptability of the crizotinib capsule formulation. OUTLINE: This is a dose-escalation study of crizotinib. Patients are assigned to Part A or Part B based on the treating physician's choice and availability of a reservation. After closure of Part A and Part B, patients are assigned to Part C. PART A (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) orally (PO) twice daily (BID) on days 1-21, cyclophosphamide intravenously (IV) once daily (QD) on days 1-5, and topotecan hydrochloride IV QD on days 1-5. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. PART B (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) PO BID as in Part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. PART C: Patients receive crizotinib (capsule formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. PART D: Patients receive crizotinib (microsphere formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

Conditions

Interventions

TypeNameDescription
DRUGCrizotinibGiven PO
DRUGCyclophosphamideGiven IV
DRUGDexrazoxane HydrochlorideGiven IV
DRUGDoxorubicin HydrochlorideGiven IV
OTHERLaboratory Biomarker AnalysisCorrelative studies
OTHERPharmacological StudyCorrelative studies
OTHERQuestionnaire AdministrationAncillary studies
DRUGTopotecan HydrochlorideGiven IV
DRUGVincristine SulfateGiven IV

Timeline

Start date
2013-04-29
Primary completion
2018-12-31
Completion
2018-12-31
First posted
2012-05-28
Last updated
2024-01-05
Results posted
2024-01-05

Locations

23 sites across 2 countries: United States, Canada

Source: ClinicalTrials.gov record NCT01606878. Inclusion in this directory is not an endorsement.