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

NCT ID: NCT01090466

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2016-03-16

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

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

temsirolimus

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardiff University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Chester

Role: PRINCIPAL_INVESTIGATOR

Leeds Cancer Centre at St. James's University Hospital

Locations

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Countries

United Kingdom

Other Identifiers

WCTU-TOTEM

Identifier Type: -

Identifier Source: secondary_id

ISRCTN31546330

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-007615-82

Identifier Type: -

Identifier Source: secondary_id

EU-21014

Identifier Type: -

Identifier Source: secondary_id

WCTU-SPON-417-07

Identifier Type: -

Identifier Source: secondary_id

CRUK-08/015

Identifier Type: -

Identifier Source: secondary_id

CDR0000667766

Identifier Type: -

Identifier Source: org_study_id