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

NCT01090466 | Completed Phase 1 DMC

• 7 other identifiers: CDR0000667766WCTU-TOTEMISRCTN31546330EUDRACT-2007-007615-82EU-21014WCTU-SPON-417-07CRUK-08/015
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Safety (recommended phase II dose and dose-limiting toxicities) (phase I)

• Progression-free survival at 6 months (phase I)

Secondary Outcomes (6)

• 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)

Interventions

cisplatin DRUG

gemcitabine hydrochloride DRUG

temsirolimus DRUG

pharmacological study OTHER

Eligibility Criteria

• Age: 16 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cardiff University: lead

Study Sites (1)

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urethral Neoplasms

Interventions

Cisplatin; Gemcitabine; temsirolimus

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; Urethral Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• John Chester

  Leeds Cancer Centre at St. James's University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2010
• First Posted: March 22, 2010
• Study Start: February 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: March 16, 2016
• Last Updated: February 6, 2018

Record last verified: 2018-02

Locations

GB (1)