A Study of Regorafenib in Advanced Pancreatic Cancer Patients

Inclusion Criteria:

• Adenocarcinoma of the exocrine pancreas with metastatic disease.
• The site of the primary tumor confirmed to have been within the pancreas.
• Progression on at least one prior line of chemotherapy for locally-advanced or metastatic pancreatic cancer.
• Progression while on treatment with a gemcitabine regimen for advanced pancreatic cancer, or within 12 months of treatment with gemcitabine as part of adjuvant therapy.
• Measurable disease on axial imaging.
• Age greater than or equal to 18 years.
• Life expectancy of at least 8 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. Enrollment of patients with PS = 2 will be capped at 7 patients.
• Subjects must be able to understand and be willing to sign the written informed consent form.
• Acute toxic effects except alopecia of any prior treatment must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 1 or less.
• Adequate bone marrow, renal, and liver function.
• Warfarin or heparin will be allowed provided that there is no prior evidence of underlying coagulation abnormality.
• Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
• Patients (men and women) of childbearing potential must agree to use adequate contraception
• Patient must be able to swallow and retain oral medication.

Exclusion Criteria:

• Previous assignment to treatment during this study.
• Uncontrolled hypertension.
• Active clinically significant cardiac disease.
• Cerebrovascular arterial event within 6 months.
• Evidence or history of bleeding diathesis or coagulopathy.
• Any bleeding event greater than or equal to NCI CTCAE Grade 3 within 4 weeks.
• New venous thrombotic or embolic events, such as deep vein thrombosis or pulmonary embolism within 3 months.
• Previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years are allowed.
• Patients with pheochromocytoma.
• Known history of HIV infection or current chronic or active hepatitis B or C, requiring antiviral medication.
• Ongoing infection greater than or equal to Grade 2 NCI-CTCAE v4.0.
• Symptomatic metastatic brain or meningeal tumors.
• Presence of a non-healing wound, non-healing ulcer, or bone fracture.
• Renal failure requiring dialysis.
• Dehydration Grade greater than or equal to 1 NCI-CTCAE v4.0.
• Patients with seizure disorder requiring medication.
• Persistent proteinuria greater than or equal to Grade 3 NCI-CTCAE v4.0.
• Symptomatic interstitial lung disease.
• Pleural effusion or ascites that cause respiratory compromise.
• History of organ allograft except corneal transplant.
• Known or suspected allergy or hypersensitivity to the study drugs.
• Any severe, uncontrolled malabsorption condition.
• Women who are pregnant or breast-feeding.
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study.
• Concurrent anti-cancer therapy other than study treatment (regorafenib).
• Prior use of regorafenib.
• Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days.
• Prior radiation therapy or hepatic arterial therapy is permitted if more than 4 weeks have passed since completion and measurable disease outside of the treated area is present, or if progression since treatment has occurred.
• Use of St. John's Wort.