Phase 2 Trial of Regorafenib in Patients With Recurrent Ovarian, Primary Peritoneal and Fallopian Tube Cancer
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regorafenib Treatment arm, all patients
|
Drug: regorafenib
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
|
Outcome Measures
Primary Outcome Measures
- 6 Month Progression Free Survival (PFS) [Patients will be checked for PFS after 6 months on treatment]
To evaluate the anti-tumor activity of Regorafenib as measured by progression free survival at 6 months in patients with recurrent gynecological cancers
- 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 [Patients will remain on treatment for approximately 4-6 months on average.]
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.
Secondary Outcome Measures
- Estimate Progression Free Survival [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]
To estimate progression free survival for patients treated with this regimen
- Frequency of Clinical Benefit (Stable Disease, Partial and Complete Response) [Scans will be done every 2 cycles (every 2 months) for disease assessment. Patients on average will be on treatment for 4-6 months]
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
Eligibility Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
Sponsors and Collaborators
- University of Utah
- Bayer
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HCI77685
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Period Title: Overall Study | |
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Overall Participants | 1 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
1
100%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
71
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
100%
|
| Male |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
1
100%
|
Outcome Measures
| Title | 6 Month Progression Free Survival (PFS) |
|---|---|
| Description | To evaluate the anti-tumor activity of Regorafenib as measured by progression free survival at 6 months in patients with recurrent gynecological cancers |
| Time Frame | Patients will be checked for PFS after 6 months on treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Measure Participants | 1 |
| Number [participants] |
1
100%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Patients will remain on treatment for approximately 4-6 months on average. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Measure Participants | 1 |
| Number [participants] |
1
100%
|
| Title | Estimate Progression Free Survival |
|---|---|
| Description | To estimate progression free survival for patients treated with this regimen |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study was terminated early, no analysis performed. |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Measure Participants | 0 |
| Title | Frequency of Clinical Benefit (Stable Disease, Partial and Complete Response) |
|---|---|
| Description | 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 |
| Time Frame | Scans will be done every 2 cycles (every 2 months) for disease assessment. Patients on average will be on treatment for 4-6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study was terminated early, no analysis performed. |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | All Patients | |
| Arm/Group Description | ||
All Cause Mortality |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Blood and lymphatic system disorders | ||
| anemia | 1/1 (100%) | |
| Cardiac disorders | ||
| tachycardia | 1/1 (100%) | |
| Gastrointestinal disorders | ||
| oral mucositis | 1/1 (100%) | |
| diarrhea | 1/1 (100%) | |
| General disorders | ||
| chills | 1/1 (100%) | |
| Investigations | ||
| platelet count decrease | 1/1 (100%) | |
| creatinine increased | 1/1 (100%) | |
| AST increased | 1/1 (100%) | |
| weight loss | 1/1 (100%) | |
| Metabolism and nutrition disorders | ||
| hyponatremia | 1/1 (100%) | |
| hyperglycemia | 1/1 (100%) | |
| Nervous system disorders | ||
| headache | 1/1 (100%) | |
| dizziness | 1/1 (100%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| hoarseness | 1/1 (100%) | |
| cough | 1/1 (100%) | |
| epistaxis | 1/1 (100%) | |
| Skin and subcutaneous tissue disorders | ||
| palmar-plantar eythrodysesthesia syndrome | 1/1 (100%) | |
| macular rash | 1/1 (100%) | |
| Vascular disorders | ||
| hypertension | 1/1 (100%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Theresa Werner |
|---|---|
| Organization | Huntsman Cancer Institute |
| Phone | 801-587-3486 |
| theresa.werner@hci.utah.edu |
- HCI77685