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
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
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
- Partial thromboplastin time (PTT) ≤1.5 times ULN
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Daniela Matei, M.D.
Hoosier Oncology Group
United States: Food and Drug Administration
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|