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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01090466
• Other study ID #: CDR0000667766
• Secondary ID: WCTU-TOTEMISRCTN
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 18, 2010
• Last updated: February 2, 2018
• Start date: February 2008
• Est. completion date: March 16, 2016

Study information

• Verified date: February 2018
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 16, 2016
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urethral Cancer
• Urethral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin

• gemcitabine hydrochloride

• temsirolimus

Other:
• pharmacological study

Locations

Country	Name	City	State
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England

Sponsors (1)

Lead Sponsor	Collaborator
Cardiff University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (recommended phase II dose and dose-limiting toxicities) (phase I)
Primary	Progression-free survival at 6 months (phase I)
Secondary	Pharmacokinetics (phase I)
Secondary	Safety, including tolerability and feasibility (phase II)
Secondary	Overall survival (phase II)
Secondary	Progression-free survival (time-to-event) (phase II)
Secondary	Objective (radiological) response rate according to RECIST criteria (phase II)
Secondary	Toxicity during and after treatment according to NCI CTCAE v 3.0 (phase II)