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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Renal Cell; Kidney Neoplasms	Drug: Interferon Alfa; Drug: CCI-779; Drug: Interferon Alfa and CCI-779	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	626 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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.
Study Start Date :	July 2003
Actual Primary Completion Date :	June 2006
Actual Study Completion Date :	March 2011

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: A	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.
Experimental: B	Drug: CCI-779; 25 mg of CCI-779 given Intra Venously once per week
Experimental: C	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

Outcome Measures

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Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Baseline up to Month 80 ]
   Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Baseline, monthly until tumor progression or death (up to Month 80) ]
   PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.
2. Percentage of Participants With Objective Response [ Time Frame: Baseline, every 2 months until tumor progression or death (up to Month 80) ]
   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.
3. Percentage of Participants With Clinical Benefit [ Time Frame: Baseline, every 2 months until tumor progression or death (up to Month 80) ]
   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.
4. Duration of Response (DR) [ Time Frame: Baseline, every month until tumor progression or death (up to Month 80) ]
   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.
5. Time to Treatment Failure (TTF) [ Time Frame: Baseline, every month until tumor progression or death (up to Month 80) ]
   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.
6. Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) [ Time Frame: Baseline to Month 80 ]
   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.
7. European Quality of Life Health Questionnaire (EQ-5D) - Index Score [ Time Frame: Baseline ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Sponsors and Collaborators

Pfizer

Investigators

Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

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Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Grünwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.

Grünwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ, Simantov R, Choueiri TK. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015 May;67(5):952-8. doi: 10.1016/j.eururo.2014.12.036. Epub 2015 Jan 7.

Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00065468 History of Changes
Obsolete Identifiers:	NCT00070330
Other Study ID Numbers:	3066K1-304
First Posted:	July 25, 2003
Results First Posted:	October 25, 2012
Last Update Posted:	October 25, 2012
Last Verified:	September 2012

Keywords provided by Pfizer:

Advanced Renal Cell Carcinoma; Kidney Cancer

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Interferons	Everolimus; Sirolimus; Interferon-alpha; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents