Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer
This multi-institutional phase I/II clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111|
- To find the maximum tolerated dose (MTD) for the phase II component and evaluate the safety and toxicity of the combination Sorafenib plus Topotecan in patients with recurrent or resistant epithelial ovarian cancer. [ Time Frame: Phase I ] [ Designated as safety issue: Yes ]
- To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. [ Time Frame: Phase II ] [ Designated as safety issue: No ]
- To determine the progression-free survival of patients treated with Sorafenib plus Topotecan. [ Time Frame: Phase II ] [ Designated as safety issue: No ]
- To determine the rate of clinical benefit defined as the number of patients experiencing an objective response or a CA125 response [ Time Frame: Phase II ] [ Designated as safety issue: No ]
|Study Start Date:||September 2007|
|Study Completion Date:||August 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Topotecan + Sorafenib. Assigned cohort dose for phase I (up to 12 patients); maximum tolerated dose for phase II (21 total patients).
Dose level -1: 200mg po daily Dose level 1: 400mg po daily Dose level 2: 400mg po bid
Dose is escalated until DLT observed.
4mg/m2 weekly, 3 weeks on and one week off.
OUTLINE: This is a multi-center study.
- Topotecan: 4mg/m2 weekly, 3 weeks on and one week off.
- Sorafenib: Assigned cohort dose for phase I (up to 12 patients) Maximum tolerated dose for phase II (21 total patients)
Cycles will consist of 4 weeks (28 days) with disease evaluations every 8 weeks.
Non-PD and acceptable toxicity: Patients will continue protocol therapy PD or unacceptable toxicity: Patients will discontinue protocol therapy
ECOG performance status 0-1
Life expectancy: Three (3) months
- White blood cell count (WBC) > 3 K/mm3
- Hemoglobin (Hgb) > 9 g/dL
- Platelets > 100 K/mm3
- Absolute neutrophil count (ANC) > 1.5 K/mm3
- INR < 1.5 or a PTT within normal limits. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
- No evidence or history of bleeding diathesis or coagulopathy.
- Bilirubin < 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN
- Alkaline phosphate < 2.5 x ULN
- Creatinine < 1.5 x ULN
- No history of myocardial infarction or angina pectoris or angina equivalent within 6 months prior to registration for protocol therapy (the patient may not be on anti-anginal or anti-arrhythmic medications), or have uncontrolled hypertension or congestive heart failure > class II NYHA
- No thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months.
- No pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 28 days prior to registration for protocol therapy.
- No non-pulmonary hemorrhage/bleeding event > CTCAE Grade 3 within 28 days prior to registration for protocol therapy.
|United States, Illinois|
|Medical & Surgical Specialists, LLC|
|Galesburg, Illinois, United States, 61401|
|United States, Indiana|
|Oncology Hematology Associates of SW Indiana|
|Evansville, Indiana, United States, 47714|
|Fort Wayne Oncology & Hematology, Inc|
|Fort Wayne, Indiana, United States, 46815|
|Indiana University Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|St. Vincent Hospital Cynecologic Oncology|
|Indianapolis, Indiana, United States, 46260|
|Arnett Cancer Care|
|Lafayette, Indiana, United States, 47904|
|Medical Consultants, P.C.|
|Muncie, Indiana, United States, 47303|
|United States, New York|
|Schwartz Gynecologic Oncology, PLLC|
|Brightwaters, New York, United States, 11718|
|Study Chair:||Daniela Matei, M.D.||Hoosier Oncology Group, Inc.|