The primary purpose of the study is to assess the potential benefit of combining two targeted therapies (an anti-EGF inhibitor along with an anti-VEGF inhibitor). The goal will be to determine whether the addition of Erlotinib to Avastin will improve the benefit in metastatic renal cell carcinoma with regard to time to progression, response rate, duration of response, and survival compared with Avastin alone. Since Avastin has been shown to be active in renal cancer, the goal will be to assess whether this activity can be enhanced with Erlotinib.

Condition	Treatment or Intervention	Phase
Renal Cell Cancer	Drug: Bevacizumab (Avastin)  Drug: Erlotinib Hydrochloride	Phase II

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

Criteria

Inclusion Criteria:

• Written informed consent
• Histologically confirmed RCC of clear cell histology Note: Subjects must have a predominant component (>50%) of conventional clear cell RCC with or without sarcomatoid features.
• Confirmed metastatic RCC
• Age >=18
• ECOG performance status of 0 or 1
• Life expectancy >= 3 months
• Prior nephrectomy
• Measurable disease, as defined by RECIST
• Use of an acceptable means of contraception (potentially fertile men and women)

Exclusion Criteria:

• RCC with predominantly sarcomatoid features
• Prior systemic or adjuvant therapy for RCC
• Prior radiotherapy for RCC within 28 days prior to Day 0, with the exception of single-fraction radiotherapy given for the indication of pain control
• Treatment with Avastin, Erlotinib, or other agents, either investigational or marketed, that act by either EGFR inhibition or anti-angiogenesis mechanisms
• Screening clinical laboratory values: * 24-hour urine collection with >= 1 g of protein * INR >= 1.5, except for subjects receiving warfarin therapy * Serum creatinine > 2.0 mg/dL * Serum calcium > 10 mg/dL (corrected) * Absolute neutrophil count (ANC) < 1500/uL * Platelet count < 75,000/uL * Total bilirubin > 2.0 mg/dL * AST or ALT > 5x the upper limit of normal (ULN) for subjects with documented liver metatases; > 2.5 x ULN for subjects without evidence of liver metastases * LDH > 1.5 x ULN * Hemoglobin < 9 gm/dl (may be transfused or receive epoetin alfa to maintain or exceed this level
• History of serious systemic disease, including myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure > 160/110 mmHg on medication), unstable angina, New York Heart Association Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication, or Grade II or greater peripheral vascular disease
• History of acute stroke within 6 months prior to randomization
• Patients on dialysis
• Other invasive malignancies, including bladder cancer and low-grade endometrial cancer within 5 years of randomization (other than squamous or basal cell carcinoma of the skin)
• Pregnancy or breast feeding
• Inability to comply with study and/or follow-up procedures
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
• Serious, non-healing wound, ulcer, or bone fracture
• Evidence of bleeding diathesis or coagulopathy
• History or clinical evidence of central nervous system or brain metastases
• History of bowel or gastric perforation
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0

Dana Sevilla      650-225-8010    sevilla.dana@gene.com
Petra Stull      650-225-7950    stull.petra@gene.com

California
      Stanford University Medical Center, Stanford,  California,  94305,  United States; Recruiting
      UCLA School of Medicine, Los Angeles,  California,  90095,  United States; Recruiting
      Bay Area Cancer Research Group, Concord,  California,  94520,  United States; Recruiting
      Kaiser Permanente Medical Group, San Diego,  California,  92120,  United States; Recruiting
Colorado
      UCHSC - Urologic Oncology, Aurora,  Colorado,  80010,  United States; Recruiting
Connecticut
      Bennett Cancer Center, Stamford,  Connecticut,  06902,  United States; Recruiting
Florida
      Lynn Regional Cancer Center - West, Boca Raton,  Florida,  33428,  United States; Recruiting
Louisiana
      Ochsner Cancer Institute, New Orleans,  Louisiana,  70121,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Not yet recruiting
Michigan
      Wayne State University / Harper University Hospital, Detroit,  Michigan,  48201,  United States; Recruiting
Missouri
      St. Joseph Oncology, St. Joseph,  Missouri,  64507,  United States; Recruiting
New Jersey
      The Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
New York
      Our Lady of Mercy Medical Center, Bronx,  New York,  10466,  United States; Recruiting
      NYU School of Medicine, New York,  New York,  10016,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
North Carolina
      Northwestern Carolina Oncology & Hematology, Hickory,  North Carolina,  28601,  United States; Recruiting
      Raleigh Hematology Oncology, Raleigh,  North Carolina,  27609,  United States; Recruiting
Ohio
      The Cleveland Clinic, Cleveland,  Ohio,  44195,  United States; Recruiting
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19004,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States; Recruiting

Study ID Numbers:  AVF2938g
Record last reviewed:  October 2004
Record first received:  April 15, 2004
ClinicalTrials.gov Identifier:  NCT00081614
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-09