- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01938573
Sirolimus, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Bladder Cancer
A Phase 1-2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Bladder Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
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)
SECONDARY OBJECTIVES:
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
Seattle, Washington, United States, 98101
- VA Puget Sound Health Care System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
- Histologically or cytologically confirmed carcinoma of the bladder of all histologies except neuroendocrine differentiation or squamous cell histology
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
Eligibility for phase 1 and phase 2 components:
- Phase 1 - clinical T3 or T4 or N1 or M1 cancer which is untreated or previously treated with platinum based therapy with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated
- Phase 2 - clinical T2-4 N0 or N1 untreated with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated
- Life expectancy >= 12 weeks
No prior malignancy is allowed except:
- Adequately treated basal cell or squamous cell skin cancer or
- In situ carcinoma of any site or
- Other adequately treated malignancy for which the patient is currently disease free for at least one year
- Absolute neutrophil count >= 1.5 x 10^9 cells/L
- Hemoglobin (Hgb) >= 9.0 g/dL
- Platelets >= 100,000 x 10^9/L
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
- Bilirubin and total bilirubin levels =< 1.5 x ULN
- Serum creatinine < 1.5 X institutional ULN mg/dL OR glomerular filtration rate (GFR) >= 50 mL/min
- All pre-study labs required for determination of eligibility are to be completed within 30 days prior to day -2 (or the next business day if falls on a weekend or holiday)
- X-rays and/or scans to assess all disease sites are to be completed within 30 days prior to day -2 (or the next business day if falls on a weekend or holiday)
Exclusion Criteria:
- Patients currently receiving active therapy for other neoplastic disorders
- Known parenchymal brain metastasis
- Active or symptomatic viral hepatitis or chronic liver disease
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of < 45 % at baseline, if done
- Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
- Administration of an investigational therapeutic within 30 days of cycle 1, day 1
- Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent
- Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible
- Any condition which, in the opinion of the investigator, would preclude participation in this trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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)
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Undergo cystectomy when appropriate
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Up to 28 days
|
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.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 28 days after completion of study treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Robert Montgomery, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Urinary Bladder Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Gemcitabine
- Cisplatin
- Sirolimus
Other Study ID Numbers
- 8027 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2013-01614 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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