RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with recurrent or metastatic ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer.

Condition	Intervention	Phase
recurrent ovarian epithelial cancer stage IV ovarian epithelial cancer Fallopian Tube Cancer peritoneal cavity cancer	Drug: bevacizumab  Drug: erlotinib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

Primary

• Determine the response rate in patients with recurrent or metastatic ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer treated with bevacizumab and erlotinib.

Secondary

• Determine the toxic effects of this regimen in these patients.
• Determine the median progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral erlotinib once daily on days 1-21. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to 1 of the study drugs may continue treatment with the remaining study drug alone in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 4-12 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer
• Recurrent or metastatic disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable indicator lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Must have received a platinum-containing chemotherapy regimen for primary disease
• Re-treatment with a platinum-based regimen required for patients who achieved a clinical complete response (CR) to primary therapy and then had a treatment-free interval > 12 months (i.e., platinum-sensitive) unless the patient developed a hypersensitivity to platinum
• Patients with a treatment-free interval < 12 months do not require prior chemotherapy for recurrent disease
• No evidence of CNS disease, including primary brain tumors or brain metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No history of bleeding diathesis

Hepatic

• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastasis)
• Bilirubin normal
• INR ≤ 1.5 (3 if receiving warfarin)
• No history of esophageal varices

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• Urine protein < 1+ OR
• Urine protein < 1,000 mg on 24-hour urine collection OR
• Urine protein:creatinine ratio < 1.0

Cardiovascular

• No arterial thromboembolic event within the past 6 months, including any of the following:
• Transient ischemic attack
• Cerebrovascular accident
• Unstable angina pectoris
• Myocardial infarction
• No clinically significant peripheral artery disease
• No uncontrolled hypertension
• No New York Heart Association grade II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease ≥ grade 2

Other

• Not pregnant
• No nursing during and for ≥ 3 months after study participation
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after study participation
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs (e.g., Chinese hamster ovary cell products or recombinant humanized antibodies)
• No serious or non-healing wound, ulcer, or bone fracture
• No active infection requiring parenteral antibiotics
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No gastrointestinal tract disease resulting in an inability to take oral medication
• No significant traumatic injury within the past 28 days
• No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other prior antiangiogenic agents
• No prior bevacizumab

Chemotherapy

• See Disease Characteristics
• No more than 2 prior cytotoxic chemotherapy regimens for recurrent or refractory disease (i.e., failed to achieve a clinical CR after primary therapy)
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to any indicator lesion unless disease has progressed since completion of radiotherapy

Surgery

• More than 4 weeks since prior major surgical procedure or open biopsy
• More than 1 week since prior core biopsy
• No prior surgery affecting absorption
• No concurrent major surgery

Other

• Recovered from prior therapy
• No prior epidermal growth factor receptor-directed therapy
• No prior erlotinib
• At least 30 days since prior investigational drugs
• More than 1 month since prior thrombolytic agents
• Concurrent warfarin allowed provided the following criteria are met:
• Patient is on a therapeutic stable dose of warfarin
• INR ≤ 3
• No active bleeding or pathological condition that would confer a high risk of bleeding (e.g., tumor invading adjacent organs or major blood vessels or varices that are likely to bleed)
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00126542

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      City of Hope Medical Group, Pasadena,  California,  91105,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Ottawa,  Illinois,  61350,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Oncology Care Associates, P.L.L.C., Saint Joseph,  Michigan,  49085,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
Canada, Ontario
      London Regional Cancer Program at London Health Sciences Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
      Ottawa Hospital Regional Cancer Centre - General Campus, Ottawa,  Ontario,  K1H 8L6,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting

Study chairs or principal investigators

Gini F. Fleming, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000434820; UCCRC-13576A; NCI-6759
Last Updated:  August 9, 2005
Record first received:  August 2, 2005
ClinicalTrials.gov Identifier:  NCT00126542
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23