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.