Phase 2 Trial of Regorafenib in Patients With Recurrent Ovarian, Primary Peritoneal and Fallopian Tube Cancer

Inclusion Criteria:

Age greater than or equal to 18 years. Life expectancy of at least 12 weeks (3 months).
Diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer.
Histologic or cytologic confirmation of the original primary tumor is required.

Patients must have measurable disease defined as at least one lesion that can be accurately
measured in at least one dimension with longest diameter (LD) greater than or equal to 10
mm using CT, MRI, or caliper measurements or greater than or equal to 20 mm with x-ray.

Patients must have at least one target lesion to be used to assess response on this
protocol as defined by RECIST 1.1.

Prior therapy: Patients must have had at least one prior platinum-based chemotherapeutic
regimen for management of primary disease containing Carboplatin, Cisplatin, or another
organo-platinum compound. This initial treatment may have included intraperitoneal therapy,
consolidation, non-cytotoxic agents (including anti-angiogenesis agents) or extended
therapy (i.e. maintenance therapy) administered after surgical or non-surgical assessment.

Patients are allowed to have previously received, but are not required to receive, one or
two additional cytotoxic regimens for management of recurrent disease.

Patients who have received only one prior cytotoxic regimen (platinum based regimen for
management of primary disease), must have a platinum-free interval of at least 6 months.

Patients must not have received any non-cytotoxic therapy for management of recurrent or
persistent disease, except hormonal based therapy is allowed. Patients are allowed to have
previously received, but are not required to have received non-cytotoxic therapy as part of
their primary treatment regimen.

ECOG score of 0-1. Adequate bone marrow, liver and renal function

Exclusion Criteria:

Patients who have progressed during initial platinum-based therapy in the upfront setting,
who have persistent disease after this initial platinum-based therapy, or who have
recurrence less than 6 months from adjuvant chemotherapy are excluded.

Major surgical procedure or significant traumatic injury within 28 days before start of
study medication.

Patients who have received wide field radiotherapy less than or equal to 4 weeks or limited
field radiation for palliation less than or equal to 2 weeks prior to starting study drug
or who have not recovered from side effects of such therapy Patients who have received any
continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies)
greater than or equal to 5 effective half-lives prior to starting study drug or who have
not recovered from side effects of such therapy.

Patients who have received chemotherapy or targeted anticancer therapy greater than or
equal to 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C, and 1 week for
hormone therapy) prior to starting study drug or who have not recovered from side effects
of such therapy.

Active concurrent primary malignancy or prior malignancies occurring within 3 years (except
cervical carcinoma in-situ, treated basal cell carcinoma, or superficial bladder tumor.

Use of any investigational drugs, biologics, or devices within 28 days prior to study
enrollment.

Prior use of regorafenib. Strong inducers and inhibitors of CYP3A4 and therapeutic
anticoagulation with Vitamin-K antagonists (e.g. warfarin) or with heparins and heparinoids
Women who are pregnant or breastfeeding. Uncontrolled hypertension defined as systolic
pressure greater than or equal to 140 mmHg or diastolic pressure greater than or equal to
90 mmHg despite optimal medical management.

Human immunodeficiency virus (HIV) positive diagnosis with a CD4 count of <100 mm3 or
detectable viral load within the past 3 months, and is receiving combination
anti-retroviral therapy.

Active or clinically significant cardiac disease Evidence or history of bleeding diathesis
or coagulopathy Any hemorrhage or bleeding event ≥ NCI CTCAE v4.0 Grade 3 within 4 weeks
prior to start of study medication.

Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism
within 6 months of start of study treatment.

Patients with pheochromocytoma Symptomatic metastatic brain or meningeal tumors. Ongoing
infection Presence of a non-healing wound, non-healing ulcer, or bone fracture Patient's
with a history of kidney disease or persistent proteinuria must have less than Grade 3
proteinuria per NCI CTCAE v4.0 at screening.

Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or
uncontrolled infection) that could cause unacceptable safety risks or compromise compliance
with the protocol.

Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, or small bowel resection).