Doxorubicin + BIBF 1120 in Patients for Ovarian Cancer
Drug: Doxil (Pegylated Liposomal Doxorubicin)
Drug: BIBF 1120
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Clinical Trial of Pegylated Liposomal Doxorubicin (Doxil®) in Combination With BIBF 1120 in Patients With Ovarian Cancer: Hoosier Oncology Group GYN10-149|
- Phase I: Safety and Toxicity of Treatment Regimen [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]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.
- Phase II: Objective Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]To assess response rate (objective response) in patients with recurrent or resistant epithelial ovarian cancer treated with BIBF 1120 plus PLD.
- Phase I and II: Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]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.
- Phase I and II: Clinical Benefit [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|Experimental: Doxil + BIBF 1120||
Drug: Doxil (Pegylated Liposomal Doxorubicin)
Phases I and II: 40 mg/m2 IV over 60 min (+/- 15 min) on day 1 of 28-day cycleDrug: BIBF 1120
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
OUTLINE: This is a phase I/II multi-center study.
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.
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
- 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)
- 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
- Creatinine levels ≤ 1.5 times ULN
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01485874
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Daniela Matei, M.D.||Hoosier Cancer Research Network|