Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
|Endometrial Adenocarcinoma Endometrial Adenosquamous Carcinoma Endometrial Clear Cell Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Stage III Uterine Corpus Cancer Stage IIIA Uterine Corpus Cancer Stage IIIB Uterine Corpus Cancer Stage IIIC Uterine Corpus Cancer Stage IV Uterine Corpus Cancer Stage IVA Uterine Corpus Cancer Stage IVB Uterine Corpus Cancer||Drug: Carboplatin Drug: Dasatinib Other: Laboratory Biomarker Analysis Drug: Paclitaxel||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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 ]Summary statistics and box plots will be used to describe the distributions of expression of EphA2 and its downstream signaling effectors.
- Change in pMEK expression [ Time Frame: Up to 1 year ]Change in pMEK expression will be evaluated.
- Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 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 circulating tumor cells (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.
- Overall survival [ 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.
- Progression free survival [ 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 Response Evaluation Criteria in Solid Tumors version 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.
|Actual Study Start Date:||September 20, 2011|
|Primary Completion Date:||July 31, 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.
Given IVDrug: Dasatinib
Given POOther: Laboratory Biomarker Analysis
Correlative studiesDrug: Paclitaxel
I. To evaluate pMEK and EphA2 signaling effectors in pre- and post- treatment biopsy tissues from patients with 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 and overall survival.
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 CAV-1, pAKT, 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|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert Coleman||M.D. Anderson Cancer Center|