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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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 Summary:

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
    Sponsor: City of Hope Medical Center

    Current Primary Outcome:

    • 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 ]


    Original Primary Outcome:

    • Maximum tolerated dose of dasatinib (Phase I)
    • Toxicity as measured by NCI CTCAE v3.0 (Phase I)
    • Overall survival at 1 year in patients with relapsed sarcoma (Phase II, Stratum A)


    Current Secondary Outcome:

    • 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 ]


    Original Secondary Outcome:

    • Response rate prior to consolidation therapy as measured by RECIST criteria (Phase II)
    • Progression-free survival (Phase II)
    • Exploratory correlative studies


    Information By: City of Hope Medical Center

    Dates:
    Date Received: November 7, 2008
    Date Started: September 2008
    Date Completion: September 2018
    Last Updated: February 10, 2017
    Last Verified: February 2017