Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse
OUTLINE: This is a multi-center study.
BNC105P is a novel vascular disrupting agent (VDA) with promising preclinical activity
combined with platinum or gemcitabine. The results of standard chemotherapy with carboplatin
and gemcitabine for ovarian cancer relapsing within 12 months of an initial platinum-based
regimen require improvement. This trial will determine the recommended dose and activity of
BNC105P administered with carboplatin and gemcitabine.
This trial uses a standard 3+3 design for allocating participants to a starting dose level
in Phase I.
If dose level 1 is deemed to have acceptable toxicity then dose levels 2a and 2b can be
opened at the same time. Dose level 3 will only open if both dose levels 2a and 2b are
deemed to have acceptable toxicity.
The underlying assumptions for determining the recommended doses for the triple combination
of carboplatin, gemcitabine and BNC105P are that the likely minimum doses required of each
agent are carboplatin AUC 4, gemcitabine 800 mg/m2 and BNC105P 12 mg/m2. This corresponds to
dose level 1.
PHASE II 1:1 RANDOMIZATION:
Carboplatin AUC 4 on day 1, gemcitabine 800 or 1000 mg/m2 on days 1 and 8 of a 21 day cycle
for a maximum of 6 cycles.
Carboplatin AUC 4 on day 1, gemcitabine 800 or 1000 mg/m2 on days 1 and day 8 with dose of
BNC105P as determined in phase I, on days 2 and 9 of a 21 day cycle for a maximum of 6
cycles, followed by single agent maintenance BNC105P 16 mg/m2 for a maximum of 6 additional
Minimum follow up for 12 months
ECOG Performance Status for Phase I: 0-1; ECOG Performance Status for Phase II: 0-2
Life Expectancy: Less than 12 weeks
Hematopoietic (both phases):
- Platelet count ≥ 100 x 109/L
- ANC ≥ 1.5 x 109/L
- Haemoglobin > 9g/dl (can be post transfusion)
- INR ≤ 1.5 x ULN
Hepatic (both phases):
- Total Bilirubin ≤ 1.5 x the upper limit of normal (ULN)
- ALT ≤ 2.5 x ULN
Renal (both phases):
- Creatinine clearance ≥ 55 mL/min according to Cockcroft Gault formula
- If Calculated GFR is 50 - 54 mL/min an isotopic GFR may be performed. If the isotopic
GFR is > 55ml/min, the patient will be eligible for the study but the calculated GFR
will be used for dose calculation.
Cardiovascular (both phases):
- Normal left ventricular ejection fraction (LVEF), i.e. ≥ 50% on Gated Heart Pool Scan,
or fractional shortening on echocardiogram ≥ institutional LLN performed within 2
months prior to randomisation
- Corrected QTc < 470 msec on ECG performed within 4 weeks prior to randomisation.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: Determine Maximum Tolerated Dose for Patients
To determine the recommended dose of BNC105P given with gemcitabine and carboplatin (maximum dose of BNC105P with no more than 1 DLT in 6 phase I participants)
Danny Rischin, Professor
University of Sydney
United States: Food and Drug Administration
GYN12-154 / ANZGOG-1103
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|
|University of Chicago||Chicago, Illinois 60637|