The purpose of this trial is to determine whether BIBF 1120 can be safely combined with pegylated liposomal doxorubicin (phase I), and to determine the clinical activity of the combination in patients with platinum-resistant ovarian cancer (phase II).
OUTLINE: This is a phase I/II multi-center study. Phase I: All patients will receive a fixed dose of pegylated liposomal doxorubicin (Doxil) of 40 mg/m2 administered IV every 28 days. The dose of BIBF 1120 will be escalated in successive cohorts of patients. A maximum of 12 cycles of combined therapy will be administered corresponding to maximum cumulative dose of PLD of 480 mg/m2. Continuation therapy with single agent BIBF 1120 may continue for selected patients. The escalation phase will follow the standard 3+3 design. Patients will be accrued to each dose level in cohorts of up to 3-6 evaluable patients. Escalation will continue until a DLT is observed, the highest dose level is reached, or medical judgment indicates. An expansion cohort of 3 to 6 patients will be treated at the MTD (or highest dose level if the MTD is not reached), in order to ensure tolerability of the regimen prior to initiating the Phase II component of the study. Phase II: Patients will receive a fixed dose of pegylated liposomal doxorubicin (Doxil) of 40 mg/m2 administered IV every 28 days. Patients will be treated at either dose Level +2 or the MTD dose level of BIBF 1120 as defined by the Phase I cohort. Each cycle will be 28 days. Patients will continue treatment with the combination therapy for a total of up to 12 cycles. ECOG Performance Status 0-1 Life Expectancy: Not specified Hematopoietic: * Absolute neutrophil count ≥ 1500 cells/mm3 * White cell blood count ≥ 3000 cells/mm3 * Hemoglobin ≥ 9.0 g/dL (can be post-transfusion) * Platelets ≥ 100,000/mm3 (can not be post-transfusion) Hepatic: * Aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times upper limit of normal (ULN) * Total serum bilirubin ≤ 1.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN Renal: * Creatinine levels ≤ 1.5 times ULN Cardiovascular: * Baseline left ventricular ejection fraction greater than 50% * International Normalized ratio(INR) ≤ 1.5 times ULN, except patients on stable doses of coumadin or low molecular weight heparin NOTE: Patients on stable doses of coumadin or low molecular weight heparin are eligible if anticoagulant doses have been stable and no bleeding complications were recorded. * Partial thromboplastin time (PTT) ≤1.5 times ULN This study was terminated due to drug availability and Phase II never opened.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Phases I and II: 40 mg/m2 IV over 60 min (+/- 15 min) on day 1 of 28-day cycle
Phase I: Escalating cohorts days -2 through +2, orally 100mg bid, 150mg bid, 200mg bid Phase II: MTD orally, bid, day 2 of 28-day cycle
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
University of Wisconsin
Madison, Wisconsin, United States
Phase I: Safety and Toxicity of Treatment Regimen
To find the maximum tolerated dose (MTD) to be used during the Phase II trial and evaluate the safety and toxicity of the combination BIBF 1120 plus PLD in patients with recurrent or resistant epithelial ovarian or endometrial cancer.
Time frame: 3 months
Phase II: Objective Response Rate
To assess response rate (objective response) in patients with recurrent or resistant epithelial ovarian cancer treated with BIBF 1120 plus PLD.
Time frame: 12 months
Phase I and II: Progression-Free Survival
To determine the progression-free survival of Phase I and II patients with recurrent or resistant epithelial ovarian cancer treated with BIBF 1120 plus PLD.
Time frame: 12 months
Phase I and II: Clinical Benefit
To determine the rate of clinical benefit for Phase I and II defined as: * the number of patients experiencing an objective response or * a CA125 response, in the absence of disease progression by clinical or radiographic criteria * sustained stable disease ≥ 3 months by clinical and radiographic criteria
Time frame: 12 months
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