Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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The primary objective of this study is efficacy. The primary efficacy endpoint of this study is a comparison of the overall survival of subjects treated with CCI-779 [Temsirolimus], administered intravenously [IV] once weekly and the combination of CCI-779, administered IV once weekly with Interferon Alfa [IFN alfa] subcutaneously [SC] three times per week [TIW], compared with the overall survival of subjects treated with IFN alfa (SC TIW) alone, in poor-prognosis subjects with advanced RCC.

Official Title
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A Phase 3, Three-Arm, Randomized, Open-Label Study Of Interferon Alfa Alone, CCI-779 Alone, And The Combination Of Interferon Alfa And CCI-779 In First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma.

Conditions
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Carcinoma, Renal Cell, Kidney Neoplasms

Intervention / Treatment
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* Drug: Interferon Alfa
* Drug: CCI-779
* Drug: Interferon Alfa and CCI-779


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: This study will be conducted in subjects with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have not received prior systemic therapy for their disease, Exclusion Criteria: Subjects with central nervous system (CNS) metastases Prior anticancer therapy for RCC Prior investigational therapy/agents within 4 weeks of randomization

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: Interferon Alfa<br>* Interferon alfa (Roferon) 3 MU given Sub Cutaneously three time /week for the first week, 9 MU given Sub Cutaneously three time /week for the second week, 18 MU given Sub Cutaneously three time /week thereafter.<br>|
| Experimental: B<br> | Drug: CCI-779<br>* 25 mg of CCI-779 given Intra Venously once per week<br>|
| Experimental: C<br> | Drug: Interferon Alfa and CCI-779<br>* 15 mg of CCI-779 given Intra Venously once per week; 6 MU of IFN alfa (Roferon) given Sub Cutaneously three time /week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact. | Baseline up to Month 80 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact. | Baseline, monthly until tumor progression or death (up to Month 80) | 
| Percentage of Participants With Objective Response | 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). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | Baseline, every 2 months until tumor progression or death (up to Month 80) | 
| Percentage of Participants With Clinical Benefit | Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Baseline, every 2 months until tumor progression or death (up to Month 80) | 
| Duration of Response (DR) | DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization. | Baseline, every month until tumor progression or death (up to Month 80) | 
| Time to Treatment Failure (TTF) | TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase. | Baseline, every month until tumor progression or death (up to Month 80) | 
| Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) | The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the dispersion of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed. | Baseline to Month 80 | 
| European Quality of Life Health Questionnaire (EQ-5D) - Index Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Renal Cell Carcinoma, Kidney Cancer