A Study of Regorafenib in Advanced Pancreatic Cancer Patients

This is a single arm, single stage Phase II study designed to evaluate progression free
survival (PFS) in patients with metastatic pancreatic cancer who have failed at least one
prior line of therapy and treatment with gemcitabine. This study is open at the Levine Cancer
Institute (LCI). A total of 32 patients will be enrolled over a two years. Following informed
consent and eligibility check, all patients will start oral regorafenib therapy (120 mg daily
for 3 weeks on / 1 week off; 28 day cycle) with a built-in dose escalation to 160mg after the
first cycle as tolerated, and will continue therapy until progression or patient withdrawal.
Patients will undergo radiological staging after the first two cycles of regorafenib therapy.
Patients with progressive disease will be removed from the study. Patients who have at least
stable disease will continue regorafenib therapy, at the Investigator's discretion, and will
be radiologically restaged bimonthly.

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.