TY - JOUR
T1 - A phase i trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer
T2 - An NRG Oncology/Gynecologic Oncology Group study
AU - Landrum, Lisa M.
AU - Brady, William E.
AU - Armstrong, Deborah K.
AU - Moore, Kathleen N.
AU - Disilvestro, Paul A.
AU - O'Malley, David M.
AU - Tenney, Meaghan E.
AU - Rose, Peter G.
AU - Fracasso, Paula M.
N1 - Funding Information:
Dr. Deborah Armstrong received funding from the NRG/GOG grant. Dr. Kathleen Moore is on the advisory board(s) for Genentech, Immunogen, Advaxis, Boehringer Ingelheim and Amgen. Dr. David O'Malley received funds for consulting on Genentech/Roche Advisory Board, Janssen Advisory Board, Clovis Advisory Board and Astra Zeneca Advisory Board. Dr. Paula Fracasso as stock/stock options in Bristol-Myers Squibb. As of May 1, 2014 Dr. Fracasso became an employee of Bristol-Myers Squibb Company (BMS) and as such, has stock with the company. Prior to her employment with BMS, she was a Professor of Medicine and Obstetrics and Gynecology at the University of Virginia where she is affiliated now as a Visiting Professor of Medicine and Obstetrics and Gynecology. The clinical study was done while she was a Professor at the University of Virginia.
Funding Information:
This study was supported by National Cancer Institute grants to the NRG Oncology/Gynecologic Oncology Group Grant (1 U10 CA180822) and the NRG Operations Grant (U 10CA180868). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Colorado Cancer Center-Anschutz Cancer Pavilion, Johns Hopkins University, Cleveland Clinic Foundation, Ohio State University Comprehensive Cancer Center, University of Oklahoma Health Sciences Center, University of Chicago, Women and In fants Hospital, and University ofIowa Hospitals and Clinics. Dr. Deborah Armstrong received funding from the NRG/GOG grant. Dr. Kathleen Mooreison the advisory board (s) for Genentech, Immunogen, Advaxis, Boehringer Ingelheim and Amgen. Dr. David O''Malley received funds for consulting on Genentech/Roche Advisory Board, Janssen Advisory Board, Clovis Advisory Board and Astra Zeneca Advisory Board. Dr. Paula Fracasso as stock/stock options in Bristol-Myers Squibb. As of May 1,2014 Dr. Fracasso became an employee of Bristol Myers Squibb Company (BMS) and assuch, has stock with the company. priortoher employment with BMS, she was a Professor of Medicine and Obstetrics and Gynecology at the University of Virginia where she is affiliated no was a Visiting Professor of Medicine and Obstetrics and Gynecology. The clinical study was done while she was a Professor at the University of Virginia. All other co-authors have no conflicts of interest to declare.
Funding Information:
This study was supported by National Cancer Institute grants to the NRG Oncology/Gynecologic Oncology Group Grant ( 1 U10 CA180822 ) and the NRG Operations Grant ( U 10CA180868 ). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Colorado Cancer Center — Anschutz Cancer Pavilion, Johns Hopkins University, Cleveland Clinic Foundation, Ohio State University Comprehensive Cancer Center, University of Oklahoma Health Sciences Center, University of Chicago, Women and Infants Hospital, and University of Iowa Hospitals and Clinics.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2016
Y1 - 2016
N2 - 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 (30 mg/m2, 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 (10 mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles 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 > 7 days (n = 3). At the MTD of veliparib (80 mg 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 > 7 days (n = 1), grade 3 hypertension (n = 5), and grade 5 sepsis (n = 1). Conclusions The MTD of veliparib combined with CD is 80 mg 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.
AB - 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 (30 mg/m2, 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 (10 mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles 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 > 7 days (n = 3). At the MTD of veliparib (80 mg 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 > 7 days (n = 1), grade 3 hypertension (n = 5), and grade 5 sepsis (n = 1). Conclusions The MTD of veliparib combined with CD is 80 mg 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.
KW - PARP inhibitors
KW - Thrombocytopenia
KW - VEGF inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84961155071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961155071&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2015.11.024
DO - 10.1016/j.ygyno.2015.11.024
M3 - Article
C2 - 26616225
AN - SCOPUS:84961155071
SN - 0090-8258
VL - 140
SP - 204
EP - 209
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -