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

Primary Purpose

Recurrent Bladder Carcinoma, Stage II Bladder Cancer, Stage III Bladder Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Gemcitabine Hydrochloride
Sirolimus
Cystectomy
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Bladder Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VA Puget Sound Health Care System
  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus, cisplatin, gemcitabine

Arm Description

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)

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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)
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.

Full Information

First Posted
September 4, 2013
Last Updated
September 20, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01938573
Brief Title
Sirolimus, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Bladder Cancer
Official Title
A Phase 1-2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Bladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
August 18, 2016 (Actual)
Study Completion Date
August 18, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Bladder Carcinoma, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sirolimus, cisplatin, gemcitabine
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune (RAPA), RAPAMYCIN
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Cystectomy
Intervention Description
Undergo cystectomy when appropriate
Primary Outcome Measure Information:
Title
Patients With Dose Limiting Toxicity
Description
Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data (including change from baseline).
Time Frame
Up to 28 days
Title
Percent of Patients With Pathologic Complete Response (Phase II)
Description
The study will follow an optimal two-stage Simon design based on pathologic complete response rate.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Up to 28 days after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Montgomery
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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