Sunitinib Malate Schedule 4/2 vs. Sunitinib Malate Continuous Dosing As First-Line Therapy For Metastatic Renal Cell Cancer (RCC)

Study Overview
=================
Brief Summary
-----------------
This trial has two parts. The purpose of the first part of the trial is to determine the doses of 2 drugs, sunitinib malate and interferon alfa-2b, that can be given safely in combination. This part is currently closed to enrollment. The purpose of the second part of the trial is to see if sunitinib malate given on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment cycle) is any better at delaying progression of renal cell cancer than sunitinib malate given on a continuous dosing schedule. The trial will also determine the number of patients whose cancer responds to the treatments, whether life of patients can be extended, what the side effects are of the treatments, how bothersome disease or treatment-related symptoms are to patients, and whether tests can be found that will predict which patients may or may not respond to these treatments in the future.

Official Title
-----------------
A Randomized Phase II Study Of The Efficacy And Safety Of Sunitinib Malate Schedule 4/2 vs. Sunitinib Malate Continuous Dosing As First-Line Therapy For Metastatic Renal Cell Cancer (Renal EFFECT Trial)

Conditions
-----------------
Carcinoma, Renal Cell

Intervention / Treatment
-----------------
* Drug: Sunitinib Malate Continuous Daily Dosing
* Drug: Sunitinib Malate Schedule 4/2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced renal cell carcinoma of clear cell origin or a component of clear cell histology. Measurable disease Exclusion Criteria: Prior systemic therapy of any kind for advanced renal cell cancer History of brain metastases Uncontrolled hypertension

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C<br> | Drug: Sunitinib Malate Continuous Daily Dosing<br>* Sunitinib malate starting dose 37.5 mg daily continuous daily regimen.<br>|
| Experimental: A<br> | Drug: Sunitinib Malate Schedule 4/2<br>* Sunitinib malate starting dose 50 mg per day for four weeks, followed by a two week off-drug period. This six week cycle is repeated.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression (TTP) Assessed Using Memorial Sloan-Kettering Cancer Center (MSKCC) Prognostic Factors Model | MSKCC Prognostic Factor Model assessed as low(0),intermediate(1-2) or high(=>3) based on number of criteria present such as Karnofsky performance status < 80 %, Lactate dehydrogenase > 1.5 * Upper limit of Normal,Hemoglobin < lower limit of normal, serum calcium > 10 mg/dL;Time from first diagnosis of renal cell carcinoma to start of systemic therapy of < 1 year.TTP was time from start of study treatment to first documentation of objective tumor progression or death due to cancer.TTP was calculated as (first event date minus date of first dose of study medication plus 1) divided by 30.44. | From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with atleast 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years | 
| Duration of Response (DR) | Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years | 
| Overall Survival (OS) Assessed Using MSKCC Prognostic Factors Model | MSKCC Prognostic Factor Model assessed as low (0), intermediate (1-2) or high (=>3) based upon number of criteria present. Criteria as follows: Karnofsky performance status < 80 %, Lactate dehydrogenase > 1.5 * Upper limit of Normal, Hemoglobin < lower limit of normal for local lab, Corrected serum calcium > 10 mg/dL; Time from first diagnosis of renal cell carcinoma to start of systemic therapy of < 1 year. OS was defined as time from date of start of treatment to date of death due to any cause. OS, in months, was calculated as (event date -start of treatment date + 1)/30.44. | From date of randomization until the date of first documented progression or date of death due to any cause, assessed up to a maximum of 2 years |