Sunitinib in Treating Patients With Progressive Metastatic Transitional Cell Cancer of the Urothelium

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

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

Treatments: Drug: sunitinib malate

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00397488

06-081

MSKCC-06081

Details and patient eligibility

About

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with progressive metastatic transitional cell cancer of the urothelium.

Full description

OBJECTIVES:

Primary

• Determine the response rate in patients with progressive metastatic transitional cell carcinoma of the urothelium treated with sunitinib malate.
• Determine the safety of this regimen in these patients.

Secondary

• Determine the time to disease progression in patients treated with this regimen.

  • To determine time to tumor progression (TTP) for sunitinib malate on a continuous dosing schedule for treatment of metastatic urothelial carcinoma.
  • To estimate sunitinib and SU012662 trough plasma concentration (Ctrough) data for the continuous daily schedule and to determine potential association with efficacy and safety.

Enrollment: 78 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium, including 1 of the following sites:

  • Bladder
  • Urethra
  • Ureter
  • Renal pelvis

• Progressive metastatic disease

  • Progressive disease defined as new or progressive lesions on cross-sectional imaging
  • Progressed despite prior treatment with cytotoxic chemotherapy

• Measurable disease

• Previously treated disease, as defined by the following:

  • Received treatment with 1-4 cytotoxic agents

  • Prior therapy must have included ≥ 1 of the following:

    • Cisplatin
    • Carboplatin
    • Paclitaxel
    • Docetaxel
    • Gemcitabine hydrochloride

  • Prior cytotoxic agents in the perioperative or metastatic setting allowed and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or all as part of a single regimen

• No symptomatic CNS metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 8.0 g/dL

• Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease is present)

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy)

• Creatinine ≤ 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• None of the following within the past 6 months:

  • Myocardial infarction
  • Severe or unstable angina
  • Coronary or peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Pulmonary embolism

• No ongoing cardiac dysrhythmias ≥ grade 2

• No prolonged QTc interval on baseline ECG

• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy

• No preexisting thyroid abnormality (i.e., thyroid function tests that cannot be maintained in the normal range with medication)

• No known HIV- or AIDS-related illness or other active infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy or chemotherapy
• At least 4 weeks since prior major surgery
• No other concurrent investigational drugs
• No concurrent participation in another clinical trial (supportive care trials or non-treatment trials [e.g., quality of life] allowed)
• No concurrent therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg once daily for thromboembolic prophylaxis allowed)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 1 patient group

Sunitinib

Experimental group

Description:

This is a phase II trial of Sunitinib in patients with metastatic urothelial carcinoma. Sunitinib will be administered at a dose of 50 mg orally once daily for four consecutive weeks followed by a two-week rest period for the initial population. A second cohort of patients will be enrolled, who will receive 37.5 mg of sunitinib orally, on a continuous dosing schedule. Intra-patient dose reduction may be required depending on the type and severity of individual toxicity encountered. Re-staging imaging studies will be performed after every cycle of treatment during the first 4 cycles and subsequently after every other cycle. Patients may continue on study as long as they are tolerating therapy and in the absence of disease progression.

Treatment:

Drug: sunitinib malate