Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
This pilot clinical trial studies how well dasatinib works together with paclitaxel and carboplatin in treating patients with stage III, stage IV or recurrent endometrial cancer. 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 or by stopping them from dividing. Giving dasatinib together with paclitaxel and carboplatin may kill more tumor cells.
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Endometrial Papillary Serous Carcinoma
Recurrent Endometrial Carcinoma
Stage IIIA Endometrial Carcinoma
Stage IIIB Endometrial Carcinoma
Stage IIIC Endometrial Carcinoma
Stage IVA Endometrial Carcinoma
Stage IVB Endometrial Carcinoma
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer|
- Change in EphA2 expression [ Time Frame: From baseline to up to day 14 ] [ Designated as safety issue: No ]Summary statistics and box plots will be used to describe the distributions of expression of EphA2 and its downstream signaling effectors.
- Response rate (complete [CR] or partial response [PR]) according to RECIST v. 1.1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Estimate the proportion of patients with CR and with (CR+PR) with 95% confidence intervals.
- PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ] [ Designated as safety issue: No ]Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
- OS [ Time Frame: From start of treatment to time of death, assessed up to 1 year ] [ Designated as safety issue: No ]Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
- Numbers of CTCs [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]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.
- Incidence of adverse events as assessed by CTCAE v. 4 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]Tabulated by grade and relationship to study drug, stratified by whether or not patients had prior pelvic radiation.
|Study Start Date:||September 2011|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dasatinib, paclitaxel, carboplatin)
Patients receive induction therapy comprising dasatinib PO QD for 14 days. *Beginning 7 days later, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1, and dasatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: paclitaxel
Other Names:Drug: carboplatin
Other Names:Other: laboratory biomarker analysis
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.
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).
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.
Patients receive induction therapy comprising dasatinib orally (PO) once daily (QD) for 14 days. *Beginning 7 days later, patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV on day 1, and dasatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: * Patients who have had prior external-beam pelvic or extended-field pelvic/para-aortic radiation therapy must receive treatment at a reduced dose.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01440998
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Robert L. Coleman 713-745-3357 email@example.com|
|Principal Investigator: Robert L. Coleman|
|Principal Investigator:||Robert Coleman||M.D. Anderson Cancer Center|