Sirolimus, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Bladder Cancer
|ClinicalTrials.gov Identifier: NCT01938573|
Recruitment Status : Completed
First Posted : September 10, 2013
Results First Posted : October 20, 2017
Last Update Posted : October 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Bladder Carcinoma Stage II Bladder Cancer Stage III Bladder Cancer Stage IV Bladder Cancer||Drug: Cisplatin Drug: Gemcitabine Hydrochloride Drug: Sirolimus Procedure: Cystectomy||Phase 1 Phase 2|
I. To define the maximum-tolerated dose (MTD) of sirolimus (rapamycin) combined with gemcitabine hydrochloride and cisplatin (GC). (Phase I)
II. To determine the pathologic complete response rate at cystectomy in patients with localized, muscle invasive carcinoma of the bladder (clinical tumor [T]2-4, node [N]0 or N1). (Phase II)
I. To assess the response rate to rapamycin combined with GC. (Phase I)
II. To assess effect of rapamycin with GC on deoxyribonucleic acid (DNA) damage surrogates in cancer associated stroma compared to untreated and GC treated stroma. (Phase I)
III. To assess effect of rapamycin with GC on DNA damage surrogates in cancer associated stroma compared to untreated and GC treated stroma. (Phase II)
IV. To assess toxicity of the MTD dose of rapamycin with GC. (Phase II)
OUTLINE: This is a phase I, dose de-escalation study of sirolimus followed by a phase II study.
Patients receive sirolimus orally (PO) two hours before or after grapefruit juice on day -2, cisplatin intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy as clinically appropriate after 1-4 courses of treatment.
After completion of study treatment, patients are followed up for 28 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1-2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Bladder Cancer|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||August 18, 2016|
|Actual Study Completion Date :||August 18, 2016|
Experimental: Sirolimus, cisplatin, gemcitabine
Sirolimus day -2, cisplatin 70 mg/m2 IV Day 1 and gemcitabine hydrochloride 1000 mg/m2 IV days 1 and 8 every 21 days for 4 cycles followed by cystectomy (surgery)
Drug: Gemcitabine Hydrochloride
Undergo cystectomy when appropriate
- Patients With Dose Limiting Toxicity [ Time Frame: Up to 28 days ]Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data (including change from baseline).
- Percent of Patients With Pathologic Complete Response (Phase II) [ Time Frame: 12 weeks ]The study will follow an optimal two-stage Simon design based on pathologic complete response rate.
- Incidence of Adverse Events Including Any Unfavorable and Unintended Sign, Symptom, Diagnosis, or Disease Temporally Associated With the Use of a Medicinal Product, Whether or Not Related to the Medicinal Product (Phase I and II) [ Time Frame: Up to 28 days after completion of study treatment ]Graded according to the NCI CTCAE version 4.0. Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data (including change from baseline). All adverse events resulting in discontinuation, dose modification, dosing interruption, and/or treatment delay of study drug will also be listed and tabulated by preferred term.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01938573
|United States, Washington|
|VA Puget Sound Health Care System|
|Seattle, Washington, United States, 98101|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Robert Montgomery||Fred Hutch/University of Washington Cancer Consortium|