Bevacizumab and Erlotinib in Treating Patients With Metastatic Pancreatic Cancer That Did Not Respond to Previous Treatment With Gemcitabine

OBJECTIVES:

Primary

- Evaluate the 6-month overall survival rate in patients with gemcitabine
hydrochloride-refractory metastatic pancreatic cancer treated with bevacizumab and
erlotinib hydrochloride.

- Determine the safety and toxicity of this regimen in these patients.

Secondary

- Evaluate the objective response rate in these patients.

- Evaluate time to tumor progression in these patients.

- Determine the efficacy of this regimen, in terms of the proportion of patients with ≥
50% decline in carbohydrate antigen 19-9, also called cancer antigen 19-9 (CA19-9)
biomarker, in these patients.

- Obtain sequential measurements of circulating tumor cells (micrometastases) and
endothelial cells in serum and correlate these variables with clinical outcomes (in
patients enrolled in UCSF site only).

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib hydrochloride
once daily on days 1-21. Treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.

Patients undergo blood collection at baseline and periodically during study for
biomarker/laboratory analysis, including the CA19-9 biomarker. Circulating tumor
micrometastases and endothelial cells are also measured in patients enrolled in University of
California San Francisco (UCSF) site.

After completion of study treatment, patients are followed at 30 days and at 6 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas

- Documented extrapancreatic metastases

- Radiographically measurable disease not required

- Gemcitabine hydrochloride-refractory disease

- Has undergone 1-3 prior therapies for locally advanced or metastatic disease with
≥ 1 regimen containing gemcitabine hydrochloride (alone or in combination with
other agents)

- Treatment given in the adjuvant setting (radiotherapy and/or chemotherapy,
given either concurrently or systemically) does not count as prior therapy
as long as progressive disease occurs > 6 months after completion of
treatment

- No central nervous system (CNS) or brain metastases

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- International Normalized Ratio (INR) ≤ 1.5 (except in patients receiving full-dose
warfarin)

- Bilirubin ≤ 2.0 mg/dL

- Creatinine ≤ 2.0 mg/dL

- AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if documented liver
metastases)

- Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)

- No contact lense use during and for 14 days after completion of study treatment

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- No history of other disease, metabolic dysfunction, or physical examination or
clinical laboratory finding that contraindicates use of an investigational drug or
precludes study compliance

- No history of serious systemic disease, including any of the following:

- Myocardial infarction within the past 6 months

- Stroke within the past 6 months

- Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg on medication)

- Unstable angina

- New York Heart Association class II-IV congestive heart failure

- Unstable symptomatic arrhythmia requiring medication

- Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal
supraventricular tachycardia) allowed

- Peripheral vascular disease ≥ grade 2

- No significant traumatic injury within the past 28 days

- No proteinuria (defined as urine protein:creatinine ratio ≥ 1.0 at screening)

- No clinically significant impairment of renal function

- No serious, nonhealing wound, ulcer, or bone fracture

- No evidence of bleeding diathesis or coagulopathy

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months

PRIOR CONCURRENT THERAPY:

- More than 28 days since prior major surgery or open biopsy

- More than 7 days since prior fine-needle aspiration or core biopsy

- No prior antiangiogenesis agent (e.g., bevacizumab or an oral vascular endothelial
growth factor receptor small molecule inhibitor) given together with an agent that
disrupts epidermal growth factor receptor signaling (e.g., cetuximab or erlotinib
hydrochloride) for locally advanced or metastatic pancreatic cancer

- Prior treatment with either one of the above alone allowed

- More than 4 weeks since prior and no concurrent participation in another clinical
trial

- No other concurrent antineoplastic or antitumor agents, including chemotherapy,
radiotherapy, immunotherapy, or hormonal anticancer therapy

- No concurrent major surgery

- No other concurrent investigational agents