Study Of SU011248 (Sunitinib) Given In A Continuous Daily Regimen In Patients With Advanced Renal Cell Cancer

Study Overview
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Brief Summary
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To evaluate the anti-tumor activity of SU011248 (sunitinib) in cytokine-refractory metastatic renal cell carcinoma (RCC) when administered in a continuous treatment regimen

Official Title
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A Phase 2 Efficacy And Safety Study Of SU011248 Administered In A Continuous Daily Regimen In Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell Metastasis

Intervention / Treatment
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* Drug: SU011248 (sunitinib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven renal cell carcinoma with metastases. Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). Failure of 1 prior cytokine-based therapy for metastatic disease. Patients treated with IFN-á alone must have received IFN-á for at least 4 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade 1. Adequate organ function Exclusion Criteria: Prior treatment with any systemic therapy other than 1 cytokine-based therapy. Previous treatment on a SU011248 (sunitinib) clinical trial. Major surgery, radiation therapy, or systemic therapy within 4 weeks of starting the study treatment. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated with no evidence of recurrent disease for 12 months. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Any of the following within the 12 months prior to starting the study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. Ongoing cardiac dysrhythmias of grade 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). Ongoing treatment with therapeutic doses of Coumadin (however, low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). Known human immunodeficiency virus (HIV) infection.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SU011248 (sunitinib)<br>Single-arm study | Drug: SU011248 (sunitinib)<br>* 37.5 mg/day, oral, continuous daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Complete Response[CR] + Partial Response[PR]) in Subjects | Confirmed objective responses using RECIST criteria defined as responses persisting on repeat imaging study for 2 assessments with at least 4 weeks between, and evaluating all target and non-target sites followed since baseline. Two PRs separated by an SD or NE visit in between was considered a confirmed response if the 2 PRs were > 4 weeks apart. CR=disappearance of all target lesions. PR is a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Tumor Response | Using RECIST criteria: date of 1st objective tumor response (CR or PR) subsequently confirmed to date of 1st objective tumor progression or to death due to any cause within 28 days after last dose of study medication, whichever was first. Censored on day after the date of the last oncologic assessment documenting no tumor progression. | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up | 
| Time to Tumor Progression (TTP) | Time from date of first dose of study medication to date of first documentation of objective tumor progression using RECIST criteria that occurred on treatment including within 28 days after the last dose of study medication. TTP censored on the day following the date of last oncologic assessment documenting absence of tumor progression. TTP based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group). | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up | 
| Progression Free Survival (PFS) | Using RECIST criteria: Time from date 1st dose study medication to date 1st documentation of objective tumor progression or death due to any cause occurring on treatment including within 28 days after last dose, whichever occurred 1st. Censored on day following the date of last oncologic assessment documenting absence of tumor progression. PFS based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group). | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up | 
| Overall Survival | Overall survival is time from the date of first dose of medication to the date of death due to any cause | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up | 
| Summary of FACIT Fatigue Scale Overall Score | FACIT Fatigue Scale: Overall score from 13-questionnaire, which measures fatigue / asthenia for patients with chronic, life-threatening illnesses. For each question, a patient rates his / her condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Higher scores always represent less fatigue / asthenia. Outcome based on completed questionnaires. | Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year. | 
| Change From Baseline in Euro-QoL Five Dimension (EQ-5D) Weighted Health Index | EQ-5D health status in 5 dimensions (mobility, self-care, pain / discomfort, anxiety / depression, usual activities) with a weighted health index based on general population values where 0.0=death and 1.0 = perfect health. Change: median index score at observation minus median index score at baseline. | Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year. | 
| Change From Baseline in EuroQoL Visual Analog Scale (EQ-VAS) Overall Health Thermometer Score | EQ-VAS score on the self-rated thermometer indicated the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state. Change: median score at observation minus median score at baseline. Maximum changes (increase or decrease from baseline). | Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year. |