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

Study Overview
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Brief Summary
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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.

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

Conditions
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Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: regorafenib


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regorafenib Treatment arm, all patients<br> | Drug: regorafenib<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Month Progression Free Survival (PFS) | To evaluate the anti-tumor activity of Regorafenib as measured by progression free survival at 6 months in patients with recurrent gynecological cancers | Patients will be checked for PFS after 6 months on treatment | 
| Incidence of Adverse Events (Grade 2 or Higher), Assessed According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 | To determine the nature and degree of toxicity of Regorafenib in this cohort of patients. Toxicity will be summarized by attribution: regorafenib-related adverse events grade 2 or higher will be reported. | Patients will remain on treatment for approximately 4-6 months on average. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate Progression Free Survival | To estimate progression free survival for patients treated with this regimen | At 6 months patients will be checked for PFS, and compared to the expected probability of the patient being alive and progression-free for at least 6 months | 
| Frequency of Clinical Benefit (Stable Disease, Partial and Complete Response) | To determine the frequency of clinical benefit (stable disease, partial, and complete response) according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria | Scans will be done every 2 cycles (every 2 months) for disease assessment. Patients on average will be on treatment for 4-6 months |