Sunitinib as Second-Line Therapy in Treating Patients With Locally Advanced or Metastatic Transitional Cell Cancer

A Multicentre Phase II Trial to Determine the Efficacy of the Anti-Tyrosine Kinase Sunitinib (Sutent®) as Second Line Therapy in Patients With Transitional Cell Carcinoma (TCC) of the Urothelium Which Failed or Progressed After First Line Chemotherapy for Advanced or Metastatic Disease

RATIONALE: Sunitinib 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.

PURPOSE: This phase II trial is studying sunitinib to see how well it works as second-line therapy in treating patients with locally advanced or metastatic transitional cell cancer.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter
• Intervention / Treatment: Drug: sunitinib malate

Detailed Description

OBJECTIVES:

Primary

• To determine the objective tumor response rate according to RECIST criteria in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium treated with sunitinib malate who failed or progressed after first-line chemotherapy .

Secondary

• To determine the safety of this drug.
• To determine the time to response and duration of response.
• To determine the progression-free survival and overall survival of these patients.
• To evaluate the quality of life of these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily for 4 weeks. Courses repeat every 6 weeks for 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 2 months.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Saint Cloud, France, 92211
    • Centre René Huguenin
  • Suresnes, France, 92151
    • Hôpital Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell cancer of the urothelium

  • Advanced or metastatic disease
  • Disease failed or progressed after first-line chemotherapy
• At least 1 non-irradiated measurable lesion assessed by CT scan or MRI according to RECIST
• No progressive brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in presence of liver metastases)
• Creatinine clearance ≥ 40 mL/min
• PTT and INR ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during study treatment
• No uncontrolled high BP, defined as > 150/100 mm Hg despite treatment
• No diagnosis of a second malignancy within the past 5 years, except for basal cell or squamous cell carcinoma of the skin, incidental PT2 prostate cancer found on radical cystoprostatectomy material, or carcinoma in situ of the cervix, that has been adequately treated with no evidence of recurrence in the past 12 months

• None of the following within the past 12 months:

  • Myocardial infarction
  • Severe/unstable angina pectoris
  • Coronary artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident
  • Transient ischemic attack
  • Pulmonary embolism
• At least 6 months since deep vein thrombosis
• No NCI CTCAE grade 3 hemorrhage within the past 4 weeks
• No pre-existing neuropathy ≥ NCI CTCAE grade 2
• No history of interstitial pneumonitis or pulmonary fibrosis
• No ongoing cardiac arrhythmias ≥ NCI CTCAE grade 2, atrial fibrillation of any grade, or prolongation of the QTc interval (> 450 msec for males or > 470 msec for females)
• No ongoing active infection
• No patients deprived of liberty or who are under supervision (including a trusteeship)
• No psychological, familial, sociological, or geographic condition potentially hampering compliance with study treatment and follow-up
• Patients must be affiliated to a social security system

PRIOR CONCURRENT THERAPY:

• Prior platinum-based therapy allowed
• No prior sunitinib malate
• No prior radiotherapy to ≥ 25% of marrow producing area
• Prior neoadjuvant or adjuvant chemotherapy allowed

• More than 2 weeks since prior and no concurrent oral anticoagulant agents at therapeutic doses

  • Low molecular weight heparin allowed
• At least 30 days since prior chemotherapy or radiotherapy and recovered
• No other concurrent anticancer treatment, including experimental agents, or participation in another investigational trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective response as assessed by RECIST criteria

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Quality of life
Safety
Time to response and duration of response

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Christine Theodore, MD, Hôpital Foch

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 14, 2008
• First Submitted That Met QC Criteria: November 14, 2008
• First Posted (Estimate): November 17, 2008

Study Record Updates

• Last Update Posted (Estimate): May 17, 2011
• Last Update Submitted That Met QC Criteria: May 14, 2011
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: stage III bladder cancer; recurrent bladder cancer; stage IV bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter; transitional cell carcinoma of the bladder; regional transitional cell cancer of the renal pelvis and ureter
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Ureteral Diseases; Kidney Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: CDR0000618219; FRE-CRH-06-374-M; FRE CRH-VESSU; INCA-RECF0845; EUDRACT-2008-001004-22; PFIZER-FRE-CRH-06/374/M