Trials / Terminated

TerminatedNCT00788125

Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

Dasatinib With Ifosfamide, Carboplatin, Etoposide: A Pediatric Phase I/II Trial

Status: Terminated
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 7 (actual)

Sponsor: City of Hope Medical Center · Academic / Other
Sex: All
Age: 1 Year – 25 Years
Healthy volunteers: Not accepted

Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with ifosfamide, carboplatin, and etoposide may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of dasatinib when given together with ifosfamide, carboplatin, and etoposide and to see how well they work in treating young patients with metastatic or recurrent malignant solid tumors.

Detailed description

OBJECTIVES: Primary * To determine the maximum tolerated dose (MTD) of dasatinib when given immediately following ifosfamide, carboplatin, and etoposide phosphate (D-ICE) as a re-induction regimen in young patients with metastatic or recurrent malignant solid tumors. (Phase I) * To describe and define the toxicities of D-ICE in these patients. (Phase I) * To determine the safety and feasibility of prolonged administration of single-agent dasatinib following completion of 2-6 courses of D-ICE in these patients. (Phase I) * To estimate the overall survival, progression-free survival, and time to progression in patients treated with D-ICE at the MTD followed by single-agent dasatinib. (Phase II) * To estimate the response rate to two courses of D-ICE when given at the MTD in these patients. (Phase II) Secondary * To determine the phosphotyrosine state of SRC family kinases and related signaling pathways, including FAK, STAT3, VEGFR, AKT, EGFR, KIT, EPHA2, and PDGFR, in paraffin-embedded tumor samples as measured by immunohistochemistry prior to and during treatment with dasatinib. * To assess gene expression profiling in fresh frozen tissue samples as measured by microarray analysis (Affymetrix GeneChips) at baseline to identify molecular signatures that may predict response to dasatinib. * To correlate biomarkers and molecular signatures with dasatinib dosage, toxicity, and antitumor activity. * To evaluate the effect of dasatinib on phosphorylation of SRC family kinases in peripheral blood mononuclear cell samples as a surrogate marker of response prior to treatment with dasatinib, at days 14-21 or when WBC ≥ 500/μL, during each treatment course, at the time of local control, and at the time of progression. OUTLINE: This is a multicenter, phase I, dose-escalation study of dasatinib followed by a phase II study. Patients enrolled in phase II are stratified according to disease. Patients receive D-ICE comprising oral dasatinib twice daily on days 5-21, ifosfamide IV over 1 hour and etoposide phosphate IV over 1 hour on days 1-5, and carboplatin IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy and/or surgery (consolidation therapy) after 2, 4, or 6 courses of D-ICE. After completion of consolidation therapy, patients receive oral dasatinib twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Tumor tissue and peripheral blood mononuclear cell (PBMC) samples are collected periodically for correlative laboratory studies. PBMCs are analyzed by western blotting for total and phospho-SRC, phospho-FAK, and other relevant biomarkers. Tumor tissue samples are analyzed by IHC for total and phospho-SRC, phospho-FAK, phospho-STAT3, phospho-KIT, and phospho-PDGFR, EPHA2, and VEGF. Tumor tissue samples are also analyzed by microarray gene expression profiling to define a potential molecular signature or gene expression pattern that may predict response to dasatinib. After completion of study treatment, patients are followed periodically.

Conditions

Interventions

Type	Name	Description
DRUG	carboplatin
DRUG	dasatinib
DRUG	etoposide phosphate
DRUG	ifosfamide
GENETIC	microarray analysis
GENETIC	western blotting
OTHER	immunohistochemistry staining method
OTHER	laboratory biomarker analysis
PROCEDURE	therapeutic conventional surgery
RADIATION	radiation therapy

Timeline

Start date: 2008-09-03
Primary completion: 2010-04-30
Completion: 2022-07-30
First posted: 2008-11-10
Last updated: 2023-07-14
Results posted: 2022-04-27

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00788125. Inclusion in this directory is not an endorsement.