Sorafenib and Erlotinib in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery

OBJECTIVES:

Primary

• To determine the efficacy of sorafenib tosylate in combination with erlotinib hydrochloride in patients with unresectable pancreatic cancer.

Secondary

• To determine the response rate in patients treated with this regimen.
• To determine the progression-free survival of patients treated with this regimen at 4 months.
• To evaluate the safety profile of this regimen in these patients.
• To evaluate the change in serum Ca 19-9 levels at baseline and at 8-week intervals.
• To evaluate the plasma proteomic profile at baseline and at 8 weeks to correlate with clinical parameters in order to identify potential prognostic or predictive markers.
• To analyze single-nucleotide polymorphisms on DNA obtained from pretreatment blood samples to evaluate toxicity and response to erlotinib hydrochloride.

OUTLINE: Patients receive oral sorafenib tosylate once or twice daily and oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Serum samples are collected at baseline and at 8-week intervals to measure Ca 19-9 levels, and plasma and buffy coat samples are collected at baseline and at week 8 for proteomic assessment and genotyping of single-nucleotide polymorphisms associated with response and toxicity to erlotinib hydrochloride.

After completion of study treatment, patients are followed up every 3 months.

DISEASE CHARACTERISTICS:

• Microscopically confirmed diagnosis of pancreatic adenocarcinoma

• Unresectable disease
• No neuroendocrine tumors or cystadenocarcinoma
• Measurable or evaluable disease by RECIST criteria
• No known brain metastases

• Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
• Creatinine ≤ 1.5 times ULN
• INR < 1.5 or PT/PTT normal unless patients are receiving anticoagulation treatments
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective barrier contraception before, during, and for at least 6 months after completion of study treatment
• Able to swallow whole pills
• No patients who currently smoke
• No cardiac disease, including any of the following:

• NYHA class III-IV congestive heart failure
• Unstable angina (anginal symptoms at rest)
• New-onset angina (began within the past 3 months)
• Myocardial infarction within the past 6 months
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• No uncontrolled hypertension defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal medical management
• No arterial thrombotic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
• No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 in the past 4 weeks
• No other hemorrhage/bleeding event ≥ CTCAE grade 3 in the past 4 weeks
• No significant traumatic injury in the past 4 weeks
• No known untreated malabsorption problem (e.g., ulcerative colitis, Crohn's disease)
• No known HIV positivity or chronic hepatitis B or C
• No known or suspected allergy to sorafenib tosylate or erlotinib hydrochloride
• No active clinically serious infection > CTCAE grade 2
• No serious non-healing wound, ulcer, or bone fracture
• No evidence or history of bleeding diathesis or coagulopathy (except for cancer-related blood clots)
• No dermatitis ≥ CTCAE grade 2 at baseline
• No patients who currently smoke

PRIOR CONCURRENT THERAPY:

• No prior treatment with antiangiogenics (e.g., bevacizumab, thalidomide, marimastat, interferon alfa, vatalanib, vandetanib, ZD6126, sorafenib, semaxanib, sunitinib, axitinib)
• No more than one line of prior therapy for metastatic disease
• More than 4 weeks since prior major surgery or open biopsy
• No concurrent strong CYP34A inhibitors or inducers
• Concurrent warfarin or heparin allowed with the approval of the principal investigator