Gemcitabine Hydrochloride, Cisplatin, and Sunitinib Malate as First-Line Therapy in Treating Patients With Locally Advanced And/or Metastatic Transitional Cell Carcinoma of the Urothelium (SUCCINCT)

Study Overview
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Brief Summary
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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. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving gemcitabine hydrochloride and cisplatin together with sunitinib malate may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving gemcitabine hydrochloride and cisplatin together with sunitinib malate and to see how well it works as first-line therapy in treating patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium.

Detailed Description
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OBJECTIVES: To determine the activity, safety, and feasibility of gemcitabine hydrochloride and cisplatin in combination with sunitinib malate as first-line therapy in patients with locally advanced and/or metastatic transitional carcinoma of the urothelium. OUTLINE: This is a multicenter study. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and oral sunitinib malate once daily on days 2-15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 6 months and 1 year. Peer Reviewed and Funded or Endorsed by Cancer Research UK

Official Title
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A Phase II Single-Arm Trial to Evaluate Cisplatin and Gemcitabine Chemotherapy in Combination With Sunitinib for First-Line Treatment of Patients With Advanced Transitional Carcinoma of the Urothelium

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

Intervention / Treatment
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* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the urothelium Pure or mixed histology Upper or lower urinary tract Radiologically measurable, locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy meeting 1 of the following criteria: T4b (bladder) or T4 (renal pelvis/ureter), any N, any M Any T, N2-3, any M Any T, any N, M1 No urothelial 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 GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means) PT or INR ≤ 1.5 times ULN 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 uncontrolled hypertension No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III-IV disease), or uncontrolled or symptomatic cardiac arrhythmia No clinically significant bacterial or fungal infection No concurrent grapefruit juice 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 that have known adverse interactions with sunitinib malate (i.e., strong CYP3A4 inhibitors or inducers) No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, bacille Calmette-Guérin [BCG], yellow fever, varicella, and TY21a typhoid vaccines)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)|
|Drug: gemcitabine hydrochloride|Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)|
|Drug: sunitinib malate|Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Proportion of patients progression free at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity during and after treatment according to NCI CTCAE v 3.0 |  | 1 Year | 
| Tolerability (side effects) and feasibility of use (number of patients requiring dose delays or reduction and/or treatment withdrawal) |  | 1 year | 
| Overall survival |  | 3 years | 
| Progression-free survival (time-to-event) |  | 1 year | 
| Objective (radiological) response rate according to RECIST |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent urethral cancer, recurrent transitional cell cancer of the renal pelvis and ureter, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, posterior urethral cancer, urethral cancer associated with invasive bladder cancer, transitional cell carcinoma of the bladder, stage IV bladder cancer, recurrent bladder cancer, anterior urethral cancer