Study of SU011248 in Patients With Advanced Kidney Cancer

Study Overview
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Brief Summary
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To determine the objective tumor response of single-agent SU011248 at a dose of 50 mg orally once daily for 4 consecutive weeks and 2 weeks rest, repeated every 6 weeks in patients with metastatic Renal Cell Cancer (RCC).

Official Title
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Phase II Study Of Single-Agent SU011248 In The Treatment Of Patients With Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: SU011248 capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven renal cell carcinoma with metastases with a component of clear cell histology Exclusion Criteria: Any cellular therapy (LAK, TIL, DC), any vaccine therapy, mini-transplantation, or systemic molecular-targeting therapy for RCC.

Ages Eligible for Study
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Minimum Age: 20 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: SU-011248 capsule<br> | Drug: SU011248 capsule<br>* 50mg, PO on day 28 of each 42 day cycle, until progression or unacceptable toxicity develops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Objective Response | Based on Extramural Review Committee's assessment. Number of subjects with objective response is defined as sum of the subjects with confirmed complete response (CR) and partial response (PR) as the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response. CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycles 1-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free survival (PFS) is defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD) or death. | Day 28 of Cycle 1-4, Day 28 of even cycles after Cycle 5, and at the end of the study. Up to 28 days after the last administration of the study drug. | 
| Time To Tumor Progression (TTP) | Time to tumor progression (TTP) is defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD). | Day 28 of Cycle 1-4, Day 28 of even cycles after Cycle 5, and at the end of the study. Up to 28 days after the last administration of the study drug. | 
| Duration of Response (DR) | Duration of response (DR) is defined as the period between the day of initial confirmation of complete response (CR) or partial response (PR) and the day of initial confirmation of progressive disease (PD) or death of any cause. For subjects who were not confirmed to have PD or death of any cause during the study (including 28 days after the completion of study treatment) or before the initiation of another antitumor therapy, DR was censored on the final confirmation of progression-free condition during the study. | Day 28 of Cycle 1-4, Day 28 of even cycles after Cycle 5, and at the end of the study. Up to 28 days after the last administration of the study drug. | 
| Time to Tumor Response (TTR) | Time to tumor response (TTR) is defined as the period between the day of initial study treatment and the day of initial confirmation of complete response (CR) or partial response (PR). CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Day 28 of Cycle 1-4, Day 28 of even cycles after Cycle 5, and at the end of the study. | 
| Overall Survival Time | Overall survival time is defined as the time from the date of first dose of study treatment to the date of the death due to any cause. For subjects whose death had not been confirmed, overall survival time was censored on the last date when the subject was known to be alive. | once year. Up to 3 years after the completion of subject registration. | 
| Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires Health State Index Score | Change from Baseline: weighted health state index at each observation minus weighted health state index at baseline. The EQ-5D evaluates 5 dimensions of health. The subjects rates the severity of impairment for each dimensions on a 3-point scale (1 to 3). The digits for five dimensions were combined in a five-digit number describing the respondent's health state. Health states were converted into a weighted health state index (Range: 0 to 1). High score is indicating high health. | Day 28 of Cycle 1; Days 1 and 28 of Cycles 2-4 | 
| Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires Visual Analog Scale (VAS) | Change from Baseline: weighted health state VAS score at each observation minus weighted health state VAS score at baseline. The VAS is a self-completed scale designed to rate the subject's current health state from 0 to 100 where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. | Day 28 of Cycle 1; Days 1 and 28 of Cycles 2-4 | 
| Trough Plasma Concentration (Ctrough) of SU-011248 in First-line Treatment Population | Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Trough Plasma Concentration (Ctrough) of SU-011248 in Pretreated Population | Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration. | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Trough Plasma Concentration (Ctrough) of SU-012662 in First-line Treatment Population | SU-012662 is a metabolite of SU-011248. Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Trough Plasma Concentration (Ctrough) of SU-012662 in Pretreated Population | SU-012662 is a metabolite of SU-011248. Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 in First-line Treatment Population | SU-012662 is a metabolite of SU-011248. Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration. The Ctrough for total drug (SU-011248+SU-012662) was calculated as the mean of the Ctrough of total drug from each individual subject. | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 in Pretreated Population | SU-012662 is a metabolite of SU-011248. Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration. The Ctrough for total drug (SU011248+SU012662) was calculated as the mean of the Ctrough of total drug from each individual subject. | Days 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF) | Days 1, 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 
| Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2) | Plasma concentrations of potential pharmacodynamic markers; Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2) | Days 1, 14 and 28 of Cycle 1; Days 1 and 28 of Cycle 2; Day 28 of Cycle 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ph2, RCC, SU011248, SUNITINIB