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

• ClinicalTrials.gov Identifier: NCT00397488
• Recruitment Status: Completed
• First Posted: November 9, 2006
• Results First Posted: January 25, 2016
• Last Update Posted: January 25, 2016
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI); Pfizer
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: November 8, 2006
• First Posted Date: November 9, 2006
• Results First Submitted Date: December 17, 2015
• Results First Posted Date: January 25, 2016
• Last Update Posted Date: January 25, 2016
• Study Start Date: September 2006
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2015)

Overall Objective Response [ Time Frame: 2 years ]

Response rate as measured by RECIST criteria. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria

Original Primary Outcome Measures (submitted: November 8, 2006)

• Response rate as measured by RECIST criteria
• Safety and toxicity

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: November 8, 2006): Time to disease progression
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sunitinib in Treating Patients With Progressive Metastatic Transitional Cell Cancer of the Urothelium
• Official Title: Phase II Study of Sunitinib in Metastatic Transitional Cell Carcinoma of the Urothelium

Brief Summary

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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Bladder Cancer
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Urethral Cancer

• Intervention: Drug: sunitinib malate

Study Arms

Experimental: Sunitinib

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.

Intervention: Drug: sunitinib malate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2012): 78
• Original Enrollment (submitted: November 8, 2006): 41
• Actual Study Completion Date: February 2012
• Actual Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00397488
• Other Study ID Numbers: 06-081; MSKCC-06081
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Memorial Sloan Kettering Cancer Center
• Study Sponsor: Memorial Sloan Kettering Cancer Center

Collaborators

• National Cancer Institute (NCI)
• Pfizer

Investigators

• Principal Investigator: Dean F. Bajorin, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: December 2015