Sirolimus, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Bladder Cancer

NCT01938573 | Completed Phase 1 Results

• 3 other identifiers: 8027NCI-2013-01614P30CA015704
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the side effects and best dose of sirolimus when given together with cisplatin and gemcitabine hydrochloride and to see how well they work in treating patients with bladder cancer. Biological therapies, such as sirolimus, may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving sirolimus together with cisplatin and gemcitabine hydrochloride may be an effective treatment for bladder cancer.

Conditions

Recurrent Bladder Carcinoma; Stage II Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Patients With Dose Limiting Toxicity

  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)

  The study will follow an optimal two-stage Simon design based on pathologic complete response rate.

  12 weeks

Secondary Outcomes (1)

• 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)

  Up to 28 days after completion of study treatment

Study Arms (1)

Sirolimus, cisplatin, gemcitabine

EXPERIMENTAL

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: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Sirolimus; Procedure: Cystectomy

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroamine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Sirolimus, cisplatin, gemcitabine

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar

Sirolimus, cisplatin, gemcitabine

Sirolimus DRUG

Given PO

Also known as: Rapamune (RAPA), RAPAMYCIN

Sirolimus, cisplatin, gemcitabine

Cystectomy PROCEDURE

Undergo cystectomy when appropriate

Sirolimus, cisplatin, gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; Sirolimus; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Macrolides; Lactones; Organic Chemicals; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Bruce Montgomery
• Organization: University of Washington

rbmontgo@uw.edu

206-598-0860

Study Officials

• Robert Montgomery

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: September 10, 2013
• Study Start: October 1, 2013
• Primary Completion: August 18, 2016
• Study Completion: August 18, 2016
• Last Updated: October 20, 2017
• Results First Posted: October 20, 2017

Record last verified: 2017-09

Locations

US (2)