A Randomized Phase II Study of Bevacizumab (NSC# 704865) and Gemcitabine in Combination With Either Cetuximab (NSC# 714692) or OSI-774 (NSC# 718781) in Patients With Advanced Pancreatic Cancer

Inclusion Criteria:

- 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

- Performance status - ECOG 0-2

- More than 3 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- No history of bleeding diatheses

- 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

- Creatinine ≤ 1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Urine protein < 1+

- 24-hour urine protein < 500 mg

- 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

- 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

- No prior bevacizumab or cetuximab

- No other prior vascular endothelial growth factor inhibitors

- No prior gemcitabine

- No prior cytotoxic chemotherapy for metastatic disease

- At least 4 weeks since prior adjuvant chemotherapy (6 weeks for mitomycin or
nitrosoureas)

- At least 4 weeks since prior radiotherapy

- Must have a site of measurable disease outside the radiation port

- 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

- 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