Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00788125|
Recruitment Status : Active, not recruiting
First Posted : November 10, 2008
Last Update Posted : February 12, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Kidney Cancer Liver Cancer Lymphoma Neuroblastoma Ovarian Cancer Sarcoma Testicular Germ Cell Tumor Unspecified Childhood Solid Tumor, Protocol Specific||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||Phase 1 Phase 2|
- 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)
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||143 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dasatinib With Ifosfamide, Carboplatin, Etoposide: A Pediatric Phase I/II Trial|
|Study Start Date :||September 3, 2008|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2018|
|Experimental: Dasatinib with Ifosfamide, Carboplatin, Etoposide||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|
- Maximum tolerated dose of dasatinib (Phase I) [ Time Frame: 28 days after start of course 1 ]
- Toxicity as measured by NCI CTCAE v3.0 (Phase I) [ Time Frame: 28 days after start of course 1 ]
- Overall survival at 1 year in patients with relapsed sarcoma (Phase II, Stratum A) [ Time Frame: 1 year after start of treatment ]
- Response rate prior to consolidation therapy as measured by RECIST criteria (Phase II) [ Time Frame: Prior to consolidation therapy ]
- Progression-free survival (Phase II) [ Time Frame: 18 months after start of treatment ]
- Exploratory correlative studies [ Time Frame: Day 14-21 of dasatinib treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00788125
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|Principal Investigator:||Judith K. Sato, MD||City of Hope Comprehensive Cancer Center|