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, administered IV once weekly and the combination of CCI-779, administered IV once weekly with IFN alfa (SC TIW), compared with the overall survival of subjects treated with IFN alfa (SC TIW) alone, in poor-prognosis subjects with advanced Renal Cell Carcinoma (RCC).

The secondary objectives of this study are safety, health outcomes, and additional efficacy endpoints. The secondary efficacy endpoints of this study are an evaluation of the following endpoints in subjects treated with CCI-779, administered IV once weekly and the combination of CCI-779, administered IV once weekly with IFN alfa (SC TIW), compared with subjects treated with IFN alfa (SC TIW) alone: progression-free survival (PFS), response rate (complete response [CR] and partial response [PR]), clinical benefit rate (CR/PR/stable disease [SD]), the duration of overall response, time to treatment failure (TTF), and health outcomes measurements. In addition, subject responses across all 3 treatment arms will be evaluated based on screening tumor expression of proteins involved in AKT-mTor pathway (i.e., Akt phosphorylation, PTEN expression).

This study will evaluate the safety of subjects treated with CCI-779 and CCI-779 given in combination with IFN alfa compared with subjects treated with IFN alfa alone.

Condition	Treatment or Intervention	Phase
Carcinoma, Renal Cell Kidney Neoplasms	Drug: Interferon Alfa  Drug: CCI-779  Drug: Interferon Alfa and CCI-779	Phase III

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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.
• Subjects must have at least 3 of the following 5 prognostic factors indicating a poor prognosis: 1.) < 1 year from time of initial RCC diagnosis to randomization 2.) Karnofsky performance status of ≥ 70 3.) Hemoglobin less than the lower limit of normal 4.) Corrected calcium > 10 mg/dL (corrected calcium = total calcium - 0.707 [albumin - 3.4 g/dL]. If a laboratory reports total calcium in millimoles per liter [mmol/L], results should be converted to milligrams per deciliter [mg/dL] using 0.249 as conversion factor) 5.) Lactate dehydrogenase > 1.5 times the upper limit of normal (ULN)
• Subjects must have a Karnofsky performance status ≥ 70.
• Subject must have at least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter ≥ 10 mm when measured by spiral computerized tomography (CT, 5-mm slice thickness contiguous) or ≥ 20 mm when measured by conventional CT (10-mm slice thickness contiguous) [Lesion must be ≥ 2 times the size of the slice thickness per Response Evaluation Criteria in Solid Tumors (RECIST)].
• Age >= 18 years.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500 cells/mm3), platelet count ≥ 100 x 109/L (100,000 cells/ mm3), hemoglobin ≥8.0 g/dL (5.0 mmol/L).
• Adequate renal function (serum creatinine ≤ 1.5 times the ULN).
• Adequate hepatic function (bilirubin ≤ 1.5 times the ULN, AST ≤ 3 times the ULN [≤ 5 times the ULN if liver metastases are present]).
• Fasting serum cholesterol ≤ 350 mg/dL (9.0 mmol/L), triglycerides ≤ 400 mg/dL (4.56 mmol/L).
• Subjects receiving cytochrome P450 (CYP) 3A4 inducers or inhibitors must be on stable doses for at least 1 week prior to randomization.
• Life expectancy of at least 8 weeks.
• Signed and dated written informed consent form.

Exclusion Criteria:

• Subjects with central nervous system (CNS) metastases. Subjects with a prior history of CNS metastases will be eligible if the screening magnetic resonance imaging (MRI)/CT (with contrast) indicates no residual disease.
• Prior anticancer therapy for RCC.
• Prior investigational therapy/agents within 4 weeks of randomization.
• History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
• Not recovered from prior surgery and/or surgery or radiation therapy within 4 weeks of randomization.
• Immunocompromised subjects, including subjects known to be human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
• Active infection or serious intercurrent illness.
• Presence of unstable angina or myocardial infarction within the previous 6 months, use of ongoing maintenance therapy for life-threatening arrhythmia, known pulmonary hypertension, or pneumonitis.
• Pregnant or nursing women, women who are of childbearing potential who are not using an effective contraceptive method, or men with partners of childbearing potential who are not using an effective contraceptive method. Agree to use effective contraceptive methods, must continue for 3 months after the last dose of CCI-779. A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant.
• Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study.
• Known hypersensitivity to any of the components in the CCI-779 infusion or IFN alfa product or other medical reasons for not being able to receive adequate premedication (for example, antihistamine or anti-inflammatory agents).

Arkansas
      University of Arkansas For Medical Science, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      San Francisco Oncology Associates, San Francisco,  California,  94115,  United States; Recruiting
      UCLA Division of Hematology/Oncology, Los Angeles,  California,  90024-2828,  United States; Recruiting
      Wilshire Oncology Medical Group, Inc., La Verne,  California,  91750,  United States; Recruiting
      SouthWest Cancer Care, Poway,  California,  92064,  United States; Recruiting
      Sharp Health Care, San Diego,  California,  92123,  United States; Recruiting
      University of Southern California Regional Cancer Center, Fountain Valley,  California,  92708,  United States; Recruiting
Connecticut
      Leever Cancer Center, Waterbury,  Connecticut,  06708,  United States; Recruiting
District of Columbia
      Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
Florida
      The Center for Hematology-Oncology, Boca Raton,  Florida,  33486,  United States; Recruiting
      Comprehensive Cancer Center Specialists, Inc., Boca Raton,  Florida,  33428,  United States; Recruiting
      University of Miami, Miami,  Florida,  33136,  United States; Recruiting
Illinois
      Carle Clinic Association, Urbana,  Illinois,  61801,  United States; Recruiting
      Rush Presyterian St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
Indiana
      Hope Center, Terre Haute,  Indiana,  47802,  United States; Recruiting
      Indiana University Medical Center, Indianapolis,  Indiana,  46202,  United States; Recruiting
      Northern Indiana Cancer Research Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
Kentucky
      University of Louisville, Louisville,  Kentucky,  40202,  United States; Recruiting
Louisiana
      Ochsner Clinic Foundation, New Orleans,  Louisiana,  70121,  United States; Recruiting
Maryland
      John Hopkins Hospital Oncology Center, Baltimore,  Maryland,  21231-1000,  United States; Recruiting
      South Shore Hematology/Oncology Associates, Rockville Centre,  Maryland,  11570,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
Missouri
      Midwest Hematology Oncology Consultants, Ltd., St. Louis,  Missouri,  63136,  United States; Recruiting
      Kansas City Oncology and Hematology Group, Kansas City,  Missouri,  64131,  United States; Recruiting
      Washington University School of Medicine, St. Louis,  Missouri,  63110,  United States; Recruiting
Montana
      Hematology-Oncology Centers of the Northern Rockies, Billings,  Montana,  59101,  United States; Recruiting
      Great Falls Clinic, Great Falls,  Montana,  59405,  United States; Recruiting
New Jersey
      Summit Medical Group, Summit,  New Jersey,  07901,  United States; Recruiting
      Hematology - Oncology Assoc. of Northern NJ, PA, Morristown,  New Jersey,  07962,  United States; Recruiting
      Department of Veterans Affairs, East Orange,  New Jersey,  07018,  United States; Recruiting
New York
      University of Rochester Cancer Center, Rochester,  New York,  14642,  United States; Recruiting
      Westchester Medical Center, Valhalla,  New York,  10595,  United States; Recruiting
      C. R. Wood Cancer Center, Glens Falls,  New York,  12801,  United States; Recruiting
      Staten Island Urological Research, Staten Island,  New York,  10304,  United States; Recruiting
North Carolina
      Northwestern Carolina Hematology Oncology, PA, Hickory,  North Carolina,  28602,  United States; Recruiting
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States; Recruiting
Ohio
      Cleveland Clinical Taussing Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
      Ohio State University, Columbus,  Ohio,  43210-1228,  United States; Recruiting
Oklahoma
      University of Oklahoma, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States; Recruiting
      Penn State - Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033,  United States; Recruiting
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
South Carolina
      Charleston Hematology-Oncology, P.A., Charleston,  South Carolina,  29403,  United States; Recruiting
Tennessee
      Baptist Regional Cancer Center, Knoxville,  Tennessee,  37920,  United States; Recruiting
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232,  United States; Recruiting
Texas
      Joe Arrington Cancer Research and Treatment Center, Lubbock,  Texas,  79410,  United States; Recruiting
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
Utah
      Huntsman Cancer Institute at the University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
Virginia
      McGuire VA Medical Center, Richmond,  Virginia,  23249,  United States; Recruiting
Washington
      Yakima Regional Cancer Care Center, Yakima,  Washington,  98902,  United States; Recruiting
      Seattle Cancer Care Alliance, Seattle,  Washington,  98109-1023,  United States; Recruiting
      Virginia Mason Medical Center, Seattle,  Washington,  98101,  United States; Recruiting
Belgium
      Algemeen Ziekenhuis St. Jan, Brugge,  8000,  Belgium; Recruiting
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada; Recruiting
Canada, British Columbia
      Vancouver General Hospital, Vancouver,  British Columbia,  V5Z 3J5,  Canada; Recruiting
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada; Recruiting
Canada, Ontario
      St. Joseph's Health Care Centre, Hamilton,  Ontario,  L8N 4A6,  Canada; Recruiting
      Community Cancer Clinic, Newmarket,  Ontario,  L3Y 2P9,  Canada; Recruiting
Canada, Quebec
      Chug-L'Hotel, Cote du Palais,  Quebec,  G1R 2J6,  Canada; Recruiting
Czech Republic
      Vseobecna fakultni nemocnice, Prague,  128 08,  Czech Republic; Recruiting
      Masarykuv onkologicky ustav, Brno,  656 53,  Czech Republic; Recruiting
      Fakultni nemocnice v Motole, Prague,  150 00,  Czech Republic; Recruiting
      Hosp Pardubice, Pardubice,  532 03,  Czech Republic; Recruiting
Germany
      Uni Essen, ESSEN,  45122,  Germany; Recruiting
      Universitaet Mainz III. Medizinische Klinik, Mainz,  D-55101,  Germany; Recruiting
      Uni Marburg - Urologie, Marburg,  35033,  Germany; Recruiting
      Helios Klinikum, Wuppertal,  42283,  Germany; Recruiting
      University Klinik Bonn, Bonn,  53105,  Germany; Recruiting
      University Halle Wittemberg, Halle,  6097,  Germany; Recruiting
      Vivantes, Berlin,  10967,  Germany; Recruiting
Greece
      University Hospital, Heraklion,  Greece; Recruiting
      University Hospital of Patra, Patra,  Greece; Recruiting
      Henry Dunan Hospital, Athens,  Greece; Recruiting
Italy
      Istituto San Raffaele, Milano,  20132,  Italy; Recruiting
      IST Regina Elena, Roma,  144,  Italy; Recruiting
      IRCCS, Bari,  70126,  Italy; Recruiting
      IRCC, Candiolo,  10060,  Italy; Recruiting
Latvia
      Daugavpils Oncological Hospital, Daugavpils,  Latvia; Recruiting
      Latvian Cancer Centre, Riga,  Latvia; Recruiting
Poland
      Centralny Szpital Kliniczny, Warszawa,  00-909,  Poland; Recruiting
      Sam. Publ. Zesp. Pulm. i Onkol, Olsztyn,  10-228,  Poland; Recruiting
      Centrum Onkologii, Warszawa,  02-781,  Poland; Recruiting
      Centrum Onkologii Ziemii Lubelskiej, Lublin,  20-090,  Poland; Recruiting
      Samodzielny Szpital Kliniczny, Poznan,  61-878,  Poland; Recruiting
      Wojewodzki Szpital Specjalistyczny im. M. Kopernika,, Lodz,  93-509,  Poland; Recruiting
      Woj. Szpital Specj. nr4, Bytom,  41-902,  Poland; Recruiting
      Wojewodzki Osrodek Onkologii, Opole,  45-060,  Poland; Recruiting
      Specj. Szpital Wojewodzki, Siedlce,  08-110,  Poland; Recruiting
Russian Federation
      Cancer Research Institute, St Petersburg,  197758,  Russian Federation; Recruiting
      Kemerovo  State  Medical  Academy, Kemerovo,  650003,  Russian Federation; Recruiting
      Gertzen Moscow Cancer Scientific-Research Institute, Moscow,  125284,  Russian Federation; Recruiting
      Central Clinical Hospital of Under the Dept of the President of Russia´s Affairs, Moscow,  121356,  Russian Federation; Recruiting
      Cancer Research Center, Moscow,  115478,  Russian Federation; Recruiting
      Clinical Hospital # 62, Moscow,  143423,  Russian Federation; Recruiting
      Cancer Research Center, Moscow,  115478,  Russian Federation; Recruiting
      Botkin City Clinical Hospital, Moscow,  125284,  Russian Federation; Recruiting
      Leningrad regional Oncology dispensary, St Petersburg,  188663,  Russian Federation; Recruiting
      Multidicipline City Hospital # 2, St Petersburg,  194354,  Russian Federation; Recruiting
      Central Scientific Research Radiology Institute, St Petersburg,  197758,  Russian Federation; Recruiting
      Medical Radiology Research Center, Obninsk,  249036,  Russian Federation; Recruiting
      Altay Oncology Center, Barnaul,  656052,  Russian Federation; Recruiting
      G.G Kuvatov Republican Clinical Hospital, Ufa,  450005,  Russian Federation; Recruiting
Singapore
      John Hopkins - NUH Singapore, Singapore,  119074,  Singapore; Recruiting
Slovakia
      National Cancer Institute, Bratislava,  833 10,  Slovakia; Recruiting
      Municipal Hospital, Zlina,  012 07,  Slovakia; Recruiting
      University Hospital Martin, Martin,  3659,  Slovakia; Recruiting
      Hospital of F.D. Roosevelt, Banska Bystrica,  97517,  Slovakia; Recruiting
South Africa
      University of Stellenbosch, Cape Town,  7505,  South Africa; Recruiting
      Johannesburg General Hospital, Johannesburg,  2197,  South Africa; Recruiting
Spain
      Hospital Clinic i Provincial, Barcelona,  8036,  Spain; Recruiting
      H. San Pablo, Barcelona,  8025,  Spain; Recruiting
      Central de Asturias, Oviedo,  33006,  Spain; Recruiting
      Hospital Clínico San Carlos, Madrid,  28040,  Spain; Recruiting
Sweden
      Sahlgrenska Universitetssjukhuset, Göteborg,  41345,  Sweden; Recruiting
      Karolinska sjukhuset, Stockholm,  171 76,  Sweden; Recruiting
Turkey
      Istanbul University Cerrahpasa Medicine Faculty, Istanbul,  Turkey; Recruiting
      Istanbul University, Istanbul,  Turkey; Recruiting
      Ege University, Izmir,  35100,  Turkey; Recruiting
Ukraine
      Kiev City Onclogical Hospital, Kiev,  03 142,  Ukraine; Recruiting
      Donetsk Regional Center, Donetsk,  83 092,  Ukraine; Recruiting
      Regional Clinical Hospital, Zaporozhye,  69103,  Ukraine; Recruiting
      Research Site, Kharkov,  61 037,  Ukraine; Recruiting
      Oblast Clinical hospital, Dnietropetrovsk,  Ukraine; Recruiting
      Lviv State Regional Centre, Lviv,  Ukraine; Recruiting
United Kingdom
      Newcastle General Hospital, Newcastle upon Tyne,  NE4 6BE,  United Kingdom; Recruiting
      Royal Marsden Hospital, London,  SM2 5PT,  United Kingdom; Recruiting
Yugoslavia
      Institute for Oncology, BELGRADE,  11000,  Yugoslavia; Recruiting
      Institute for Oncology, Sremska Kamenica,  21204,  Yugoslavia; Recruiting

Study ID Numbers:  3066K1-304-WW
Record last reviewed:  September 2004
Record first received:  July 24, 2003
ClinicalTrials.gov Identifier:  NCT00065468
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29