RATIONALE: Monoclonal antibodies, such as cetuximab and bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining bevacizumab and gemcitabine with either cetuximab or erlotinib may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying bevacizumab, gemcitabine, and cetuximab to see how well they work compared to bevacizumab, gemcitabine, and erlotinib in treating patients with advanced pancreatic cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas recurrent pancreatic cancer stage II pancreatic cancer stage III pancreatic cancer stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: bevacizumab  Drug: cetuximab  Drug: erlotinib  Drug: gemcitabine  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  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:

• Compare the objective response rate in patients with advanced adenocarcinoma of the pancreas treated with bevacizumab and gemcitabine with cetuximab vs erlotinib.
• Compare the toxicity of these regimens in these patients.
• Compare median progression-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center (University of Chicago vs other) and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22; gemcitabine IV over 30 minutes on days 1, 8, and 15; and bevacizumab IV over 30-90 minutes on days 1 and 15.
• Arm II: Patients receive gemcitabine and bevacizumab as in arm I. Patients also receive oral erlotinib once daily on days 1-5, 8-12, and 15-26. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 54-126 patients (27-63 per treatment arm) will be accrued for this study within 16 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Advanced disease
• Patients with locally advanced disease must have disease that extends outside the boundaries of a standard radiation port
• Not amenable to curative surgery or radiotherapy
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Pleural effusions and ascites are not considered measurable lesions
• No CNS disease, including primary brain tumors or brain metastasis
• No tumor invasion into the duodenum

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

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

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
• INR ≤ 1.5 (≤ 3 for patients on warfarin)
• No esophageal varices

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• Urine protein < 1+ OR
• 24-hour urine protein < 500 mg

Cardiovascular

• No history of a recent cerebrovascular accident
• No clinically significant cardiovascular disease
• No uncontrolled hypertension
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease ≥ grade II
• None of the following arterial thromboembolic events within the past 6 months:
• Transient ischemic attack
• Cerebrovascular accident
• Unstable angina
• Myocardial infarction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation
• HIV negative
• No significant traumatic injury within the past 28 days
• No gastrointestinal tract disease resulting in an inability to take oral medication
• No allergic reactions to compounds similar to bevacizumab, cetuximab, or erlotinib (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 antibiotics
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior bevacizumab or cetuximab
• No other prior vascular endothelial growth factor inhibitors

Chemotherapy

• No prior gemcitabine
• No prior cytotoxic chemotherapy for metastatic disease
• At least 4 weeks since prior adjuvant chemotherapy (6 weeks for mitomycin or nitrosoureas)

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy
• Must have a site of measurable disease outside the radiation port

Surgery

• No prior surgical procedure affecting absorption
• More than 28 days since prior major surgical procedure or open biopsy
• More than 7 days since prior core biopsy
• No concurrent major surgical procedures

Other

• No prior erlotinib
• No other prior epidermal growth factor receptor inhibitors
• At least 30 days since prior investigational drugs
• More than 1 month since prior thrombolytic agents
• Concurrent warfarin or low molecular weight heparin allowed provided the following criteria are met:
• Currently therapeutic on a stable dose
• INR target range ≤ 3
• Patients undergo weekly INR testing
• No evidence of active bleeding or pathological condition that carries high risk of bleeding (e.g., tumor invading adjacent organs or esophageal varices)
• No concurrent chronic daily therapy with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function
• No other concurrent antiplatelet medications
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapies or agents
• No other concurrent investigational drugs

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
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      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
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10467,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting

Study chairs or principal investigators

Hedy L. Kindler, MD,  Principal Investigator,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000383145; UCCRC-13200A; NCI-6580; NCT00091026
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  September 7, 2004
ClinicalTrials.gov Identifier:  NCT00091026
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08