Safety And Effectiveness Of Daily Dosing With 37.5 mg Sunitinib Malate In Patients With Advanced Kidney Cancer

Study Overview
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Brief Summary
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A phase II study to allow patients with advanced kidney cancer access to sunitinib malate treatment and to find out the good and bad effects of taking 37.5 mg sunitinib malate in a continuous daily regimen (once per day) for one year.

Official Title
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A Phase II Efficacy And Safety Study Of Sunitinib Malate (SU011248) Administered In A Continuous Daily Regimen In Patients With Advanced (First-Line) Renal Cell Cancer

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Sunitinib malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced kidney cancer Exclusion Criteria: Previous treatment for kidney cancer, except surgical removal of kidney tumor
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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SUNITINIB MALATE.<br>Sunitinib malate starting dose 37.5 mg daily continuous daily schedule | Drug: Sunitinib malate<br>* Sunitinib malate starting dose 37.5 mg daily continuous daily schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Overall Confirmed Objective Response (OR) | OR = subjects with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) persisting > = 4 weeks after initial documentation of response. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DR) | Time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the end date for DR minus first CR or PR that was subsequently confirmed +1]/7. | From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter or death due to any cause | 
| Time to Tumor Progression (TTP) | Time from date of first dose of study medication to first documentation of objective tumor progression. The 50% quartile point estimate is provided. The criteria for tumor progression was according to RECIST. | From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter | 
| Progression-Free Survival (PFS) | Time from start of study medication to first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in months) was calculated as (first event date minus first dose date +1)/7. | From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter or death | 
| 1-Year Survival | One year survival rate defined as the probability that a subject was alive 1 year after the date of first study treatment. | From start of treatment through Day 1 of Weeks 5, 9, and every 8 weeks thereafter up until 1 year | 
| Trough Plasma Concentrations (Ctrough) of Sunitinib | Ctrough = the concentration prior to study drug administration. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by CR or PR Versus Progressive Disease (PD) for Sunitinib | Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by Tumor Response (CR or PR or [Stable Disease (SD) > = 12 Weeks] Versus PD) for Sunitinib | Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough of SU-012662 (Sunitinib's Metabolite) | Ctrough = the concentration prior to study drug administration. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by CR or PR Versus PD for SU-012662 (Sunitinib's Metabolite) | Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) for SU-012662 (Sunitinib's Metabolite) | Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough of Total Drug (Sunitinib + SU-012662) | Ctrough = the concentration prior to study drug administration. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by CR or PR Versus PD for Total Drug (Sunitinib + SU012662) | Summary statistics of ctrough at each time point by group (CR or PR versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) for Total Drug (Sunitinib + SU012662) | Summary statistics of ctrough at each time point by group (CR or PR or SD versus PD) are presented. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Ctrough Correlated With Serious Adverse Events (SAEs) | Serious adverse event defined as any untoward medical occurrence at any dose that: Results in death; Is life-threatening (immediate risk of death); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Results in congenital anomaly/birth defect. | Predose on Day 1 of Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53 | 
| Vascular Endothelial Growth Factor (VEGF) Concentration at Baseline |  | Baseline | 
| VEGF at Baseline Stratified by Tumor Response (CR or PR Versus PD) | Summary statistics of VEGF at baseline by group (CR or PR versus PD) are presented. | Baseline (Cycle 1, Day 1) | 
| VEGF at Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) | Summary statistics of VEGF at baseline by group (CR or PR or SD versus PD) are presented. | Baseline (Cycle 1, Day 1) | 
| VEGF Ratio to Baseline at Each Time Point | VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline). | Baseline to Day 1 of Weeks 3 through 53 | 
| VEGF Ratio to Baseline Stratified by Tumor Response (CR or PR Versus PD) | Median VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR versus PD). | Baseline to Day 1 of Weeks 3 through 53 | 
| VEGF Ratio to Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) | Median VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 12 weeks] versus PD). | Baseline to Day 1 of Weeks 3 through 53 | 
| Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline |  | Baseline | 
| sVEGFR2 at Baseline Stratified by Tumor Response (CR or PR Versus PD) | Summary statistics of sVEGFR2 at baseline by group (CR or PR versus PD) are presented. | Baseline (Cycle 1, Day 1) | 
| sVEGFR2 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) | Summary statistics of sVEGFR2 at baseline by group (CR or PR or SD versus PD) are presented. | Baseline (Cycle 1, Day 1) | 
| sVEGFR2 Ratio to Baseline at Each Time Point | sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline). | Baseline to Day 1 of Weeks 3 through 53 | 
| sVEGFR2 Ratio to Baseline Stratified by Tumor Response (CR or PR Versus PD) | Median sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR versus PD). | Baseline to Day 1 of Weeks 3 through 53 | 
| sVEGFR2 Ratio to Baseline Stratified by Tumor Response (CR or PR or [SD > = 12 Weeks] Versus PD) | Median sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 12 weeks] versus PD). | Baseline to Day 1 of Weeks 3 through 53 | 
| Patient-Assessed Fatigue | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Scale: Overall score from 13-question questionnaire (measures fatigue/asthenia for patients with chronic, life-threatening illnesses). For each question, patient rates condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Total FACIT-Fatigue score = sum score of the 13 question scores; total range: 0 - 52; higher total score represents less fatigue. End of treatment assessment was for subjects who completed the study only. | Baseline (Day 1, Week 1), Day 1 of Weeks 3, 5, 7, 9, 11, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, Week 53 (End of Treatment) | 
| Cancer Related Symptoms, Well-Being, and Concerns | FACT-Advanced Kidney Cancer Symptom Index (FKSI) Questionnaire: subscale designed to be a stand-alone instrument to measure symptoms and quality of life in patients with advanced kidney cancer. Contains 15 questions. Each question was answered on a 5-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Total FKSI score = sum score of the 15 item scores; total range: 0 - 60; 0 (most severe symptoms and concerns) to 60 (no symptoms or concerns). End of treatment assessment was for subjects who completed the study only. | Baseline (Day 1, Week 1), Day 1 of Weeks 3, 5, 7, 9, 11, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, Week 53 (End of Treatment) |