Abstract
A phase I trial of pegylated liposomal doxorubicin (PLD),
carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive
ovarian, primary peritoneal, and fallopian tube cancer: An NRG
Oncology/Gynecologic Oncology Group study
OBJECTIVE:
To
determine the maximum tolerated dose (MTD) and dose-limiting toxicities
(DLTs) of
veliparib combined with PLD and carboplatin (CD) in patients
with recurrent, platinum-sensitive epithelial ovarian cancer.
To
determine the tolerability at the MTD combined with bevacizumab.
METHODS:
Patients received PLD (30mg/m
2,
IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7
(intermittent) or days 1-28 (continuous). Standard 3+3 design was used
in the dose escalation phase with DLTs based on the first cycle. Once
the MTDs were determined,
cohorts of 6 patients were enrolled to each
regimen with bevacizumab (10mg/kg on days 1 and 15) to assess
feasibility. DLTs were based on the first 4cycles of treatment in the
bevacizumab cohorts.
RESULTS:
In
the dose-escalation phase, 27 patients were treated at 3 dose levels
with DLTs noted in 6 patients including
grade 4 thrombocytopenia (n=4),
and prolonged neutropenia >7days (n=3). At the MTD of veliparib (80mg
p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At
MTD, 12 additional patients were treated with bevacizumab with 9
patients experiencing DLTs including
grade 4 thrombocytopenia (n=4),
prolonged neutropenia >7days (n=1), grade 3 hypertension (n=5), and
grade 5 sepsis (n=1).
CONCLUSIONS:
The
MTD of veliparib combined with CD is 80mg p.o. b.i.d. in women with
recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs
were noted in 9 out of 12 patients. Lower doses of veliparib will need
to be considered when given in combination with platinum-based
therapies.
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