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Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium

Primary Purpose

Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
cisplatin
gemcitabine hydrochloride
temsirolimus
pharmacological study
Sponsored by
Cardiff University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring transitional cell carcinoma of the bladder, recurrent bladder cancer, recurrent urethral cancer, recurrent transitional cell cancer of the renal pelvis and ureter, stage IV bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, distal urethral cancer, proximal urethral cancer, urethral cancer associated with invasive bladder cancer, stage IV urethral cancer

Eligibility Criteria

16 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically confirmed transitional cell carcinoma of the urothelium

    • Pure or mixed histology
    • Upper or lower urinary tract
  • Radiologically evaluable* locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy, meeting any 1 of the following criteria:

    • T4b, any N, any M
    • Any T, N2-3, any M
    • Any T, any N, M1
  • NOTE: *Patients enrolled in the phase II portion of the trial must have radiologically measurable disease.
  • No transitional cell cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
  • No history of CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and ALP ≤ 2.5 times ULN
  • PT or INR ≤ 1.5
  • GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Fit to receive cisplatin-containing combination chemotherapy
  • No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
  • No known HIV positivity or chronic hepatitis B or C infection
  • No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or symptomatic cardiac arrhythmia
  • No clinically significant bacterial or fungal infection

PRIOR CONCURRENT THERAPY:

  • At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
  • At least 1 month since prior investigational drug
  • No prior systemic therapy for locally advanced or metastatic disease

    • Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression are eligible
  • No concurrent anticoagulant therapy with warfarin or unfractionated heparin

    • Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
  • No concurrent medications which have known adverse interactions with the treatment used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial)
  • No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, Bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)
  • No concurrent grapefruit juice

Sites / Locations

  • Leeds Cancer Centre at St. James's University Hospital

Outcomes

Primary Outcome Measures

Safety (recommended phase II dose and dose-limiting toxicities) (phase I)
Progression-free survival at 6 months (phase I)

Secondary Outcome Measures

Pharmacokinetics (phase I)
Safety, including tolerability and feasibility (phase II)
Overall survival (phase II)
Progression-free survival (time-to-event) (phase II)
Objective (radiological) response rate according to RECIST criteria (phase II)
Toxicity during and after treatment according to NCI CTCAE v 3.0 (phase II)

Full Information

First Posted
March 18, 2010
Last Updated
February 2, 2018
Sponsor
Cardiff University
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1. Study Identification

Unique Protocol Identification Number
NCT01090466
Brief Title
Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium
Official Title
A Phase I/II Single-Arm Trial to Evaluate the Combination of Cisplatin and Gemcitabine With the mTOR Inhibitor Temsirolimus for First-Line Treatment of Patients With Advanced Transitional Cell Carcinoma of the Urothelium
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
March 16, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cardiff University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and cisplatin together with temsirolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus given together with gemcitabine hydrochloride and cisplatin as first-line therapy in treating patients with locally advanced and/or metastatic transitional cell cancer of the urothelium.
Detailed Description
OBJECTIVES: Primary To determine a safety profile of temsirolimus in combination with cisplatin and gemcitabine hydrochloride, including dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD) in patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. (phase I) To determine the recommended dose for the Phase II stage of the trial and subsequent studies. (phase I) To assess progression-free survival (PFS) at six months from date of enrollment. (phase II) Secondary To determine the pharmacokinetic profile of temsirolimus in combination with cisplatin and gemcitabine hydrochloride. (phase I) To determine tolerability (side-effects) and feasibility (number of participants requiring dose delays or reduction and/or treatment withdrawal). (phase II) To determine objective response rate as assessed by RECIST. (phase II) To assess PFS of these patients. (phase II) To assess overall survival of these patients. (phase II) To determine toxicity during and after treatment in these patients. (phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of temsirolimus followed by a phase II study. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and temsirolimus IV over 30 minutes on days 1 or 2, 8 or 9, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Blood specimens may be collected periodically for pharmacokinetic studies. After completion of study treatment, patients are followed at 6 months and 1 year. Peer Reviewed and Funded or Endorsed by Cancer Research UK

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer
Keywords
transitional cell carcinoma of the bladder, recurrent bladder cancer, recurrent urethral cancer, recurrent transitional cell cancer of the renal pelvis and ureter, stage IV bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, distal urethral cancer, proximal urethral cancer, urethral cancer associated with invasive bladder cancer, stage IV urethral 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
15 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Type
Drug
Intervention Name(s)
temsirolimus
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Safety (recommended phase II dose and dose-limiting toxicities) (phase I)
Title
Progression-free survival at 6 months (phase I)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (phase I)
Title
Safety, including tolerability and feasibility (phase II)
Title
Overall survival (phase II)
Title
Progression-free survival (time-to-event) (phase II)
Title
Objective (radiological) response rate according to RECIST criteria (phase II)
Title
Toxicity during and after treatment according to NCI CTCAE v 3.0 (phase II)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the urothelium Pure or mixed histology Upper or lower urinary tract Radiologically evaluable* locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy, meeting any 1 of the following criteria: T4b, any N, any M Any T, N2-3, any M Any T, any N, M1 NOTE: *Patients enrolled in the phase II portion of the trial must have radiologically measurable disease. No transitional cell cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease No history of CNS metastases PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT and ALP ≤ 2.5 times ULN PT or INR ≤ 1.5 GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Fit to receive cisplatin-containing combination chemotherapy No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer No known HIV positivity or chronic hepatitis B or C infection No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III or IV disease), or uncontrolled or symptomatic cardiac arrhythmia No clinically significant bacterial or fungal infection PRIOR CONCURRENT THERAPY: At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume At least 1 month since prior investigational drug No prior systemic therapy for locally advanced or metastatic disease Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression are eligible No concurrent anticoagulant therapy with warfarin or unfractionated heparin Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin No concurrent medications which have known adverse interactions with the treatment used on this trial (e.g., CYP3A4 inhibitors or inducers in phase I of this trial) No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, Bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines) No concurrent grapefruit juice
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Chester
Organizational Affiliation
Leeds Cancer Centre at St. James's University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leeds Cancer Centre at St. James's University Hospital
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Gemcitabine Hydrochloride, Cisplatin, and Temsirolimus as First-Line Therapy in Treating Patients With Locally Advanced and/or Metastatic Transitional Cell Cancer of the Urothelium

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