Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01440998|
Recruitment Status : Completed
First Posted : September 27, 2011
Last Update Posted : April 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Adenocarcinoma Endometrial Clear Cell Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Stage III Uterine Corpus Cancer AJCC v7 Stage IIIA Uterine Corpus Cancer AJCC v7 Stage IIIB Uterine Corpus Cancer AJCC v7 Stage IIIC Uterine Corpus Cancer AJCC v7 Stage IV Uterine Corpus Cancer AJCC v7 Stage IVA Uterine Corpus Cancer AJCC v7 Stage IVB Uterine Corpus Cancer AJCC v7||Drug: Carboplatin Drug: Dasatinib Other: Laboratory Biomarker Analysis Drug: Paclitaxel||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer|
|Actual Study Start Date :||September 20, 2011|
|Actual Primary Completion Date :||December 31, 2015|
|Actual Study Completion Date :||December 31, 2015|
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: Laboratory Biomarker Analysis
- Change in pMEK expression [ Time Frame: Up to 1 year ]Change in pMEK expression will be evaluated.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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): NCT01440998
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert Coleman||M.D. Anderson Cancer Center|