Phase 2 Trial of Regorafenib in Patients With Recurrent Ovarian, Primary Peritoneal and Fallopian Tube Cancer
Condition: Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer
MeSH terms: Fallopian Tube Neoplasms
Intervention: regorafenib
Intervention description: Patients will be treated with Regorafenib 160 mg (4 x 40 mg tablets) daily for 21 days of a 28 day cycle (three weeks on drug, one week off) until disease progression or adverse effects prohibit further treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This will be a non-blinded, single arm study to test the efficacy of Regorafenib in patients
      with recurrent ovarian, primary peritoneal, and fallopian tube cancer.
    

Eligibility criteria:

        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).