Clinical Trial: Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

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

Official Title: Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer

Brief Summary: This pilot clinical trial studies how well dasatinib works together with paclitaxel and carboplatin in treating patients with stage III, stage IV or endometrial cancer that has come back after a period of improvement. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving dasatinib together with paclitaxel and carboplatin may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the impact of dasatinib on ephrin type-A receptor 2 (EphA2) expression in tissue biopsies from patients with previously untreated, advanced-staged, measurable primary or recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4 (CTCAE v. 4) of dasatinib administered in combination with paclitaxel and carboplatin in patients with advanced-staged measurable primary or recurrent endometrial cancer.

II. To record the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

III. To describe the progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

I. To explore the relationship of micro ribonucleic acid (RNA) 520d-3p (miR520d-3p) and EphA2 in pretreatment biopsies.

II. To evaluate downstream EphA2 signaling effectors, such as focal adhesion kinase (FAK), paxillin, and p130cas in pre- and post-tissue treatment biopsies.

III. To explore the effect of dasatinib on the expression of other Eph family members such as EphB2 and EphB4.

IV. To quantify circulating tumor cells (CTCs) before and during the individual treatment phases.

OUTLINE:

Patients receive induction therapy comprising dasatinib orally (PO) once daily (QD) for 14
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Change in EphA2 expression [ Time Frame: From baseline to up to day 14 ]

Summary statistics and box plots will be used to describe the distributions of expression of EphA2 and its downstream signaling effectors.


Original Primary Outcome: Impact of dasatinib on EphA2 expression in metastatic or recurrent endometrial cancer tissues

Current Secondary Outcome:

  • Incidence of adverse events as assessed by CTCAE v. 4 [ Time Frame: Up to 1 year ]
    Tabulated by grade and relationship to study drug, stratified by whether or not patients had prior pelvic radiation.
  • Numbers of CTCs [ Time Frame: Up to 1 year ]
    Descriptive statistics will be used to summarize the number of CTCs for patients with each type of response. Estimate the mean number of CTCs for each of these groups with 95% confidence intervals.
  • OS [ Time Frame: From start of treatment to time of death, assessed up to 1 year ]
    Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
  • PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ]
    Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
  • Response rate (complete [CR] or partial response [PR]) according to RECIST v. 1.1 [ Time Frame: Up to 1 year ]
    Best overall response will be tabulated. The proportion of patients with CR and with (CR+PR) will be estimated with 95% confidence intervals.


Original Secondary Outcome:

  • Response rate (complete or partial response)
  • PFS and OS
  • Toxicity


Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 24, 2011
Date Started: September 2011
Date Completion:
Last Updated: December 22, 2015
Last Verified: December 2015