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

• Progression-Free Survival (PFS) [ Time Frame: Baseline, monthly until tumor progression or death (up to Month 80) ] [ Designated as safety issue: No ]
  PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.
• Percentage of Participants With Objective Response [ Time Frame: Baseline, every 2 months until tumor progression or death (up to Month 80) ] [ Designated as safety issue: No ]
  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.
• Percentage of Participants With Clinical Benefit [ Time Frame: Baseline, every 2 months until tumor progression or death (up to Month 80) ] [ Designated as safety issue: No ]
  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.
• Duration of Response (DR) [ Time Frame: Baseline, every month until tumor progression or death (up to Month 80) ] [ Designated as safety issue: No ]
  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.
• Time to Treatment Failure (TTF) [ Time Frame: Baseline, every month until tumor progression or death (up to Month 80) ] [ Designated as safety issue: No ]
  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.
• Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) [ Time Frame: Baseline to Month 80 ] [ Designated as safety issue: Yes ]
  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.
• European Quality of Life Health Questionnaire (EQ-5D) - Index Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  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.

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.

• Carcinoma, Renal Cell
• Kidney Neoplasms

• Drug: Interferon Alfa
  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.
• Drug: CCI-779
  25 mg of CCI-779 given Intra Venously once per week
• Drug: Interferon Alfa and CCI-779
  15 mg of CCI-779 given Intra Venously once per week; 6 MU of IFN alfa (Roferon) given Sub Cutaneously three time /week

• Active Comparator: A
  Intervention: Drug: Interferon Alfa
• Experimental: B
  Intervention: Drug: CCI-779
• Experimental: C
  Intervention: Drug: Interferon Alfa and CCI-779

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