A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Benzimidazoles
/ administration & dosage
Bevacizumab
/ administration & dosage
Carboplatin
/ administration & dosage
Carcinoma, Ovarian Epithelial
/ drug therapy
Cisplatin
/ administration & dosage
Cohort Studies
Dose-Response Relationship, Drug
Fallopian Tube Neoplasms
/ drug therapy
Female
Humans
Injections, Intraperitoneal
Injections, Intravenous
Middle Aged
Ovarian Neoplasms
/ drug therapy
Paclitaxel
/ administration & dosage
Peritoneal Neoplasms
/ drug therapy
Progression-Free Survival
Ovarian cancer
PARP inhibition
Primary therapy
Veliparib
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
01
08
2019
revised:
06
10
2019
accepted:
09
10
2019
pubmed:
12
11
2019
medline:
25
2
2020
entrez:
12
11
2019
Statut:
ppublish
Résumé
Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). National Cancer Institute.
Sections du résumé
BACKGROUND
Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC.
METHODS
A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles.
FINDINGS
Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID.
INTERPRETATION
The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651).
FUNDING
National Cancer Institute.
Identifiants
pubmed: 31708167
pii: S0090-8258(19)31569-0
doi: 10.1016/j.ygyno.2019.10.012
pmc: PMC7048389
mid: NIHMS1542948
pii:
doi:
Substances chimiques
Benzimidazoles
0
veliparib
01O4K0631N
Bevacizumab
2S9ZZM9Q9V
Carboplatin
BG3F62OND5
Paclitaxel
P88XT4IS4D
Cisplatin
Q20Q21Q62J
Banques de données
ClinicalTrials.gov
['NCT00989651']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
13-22Subventions
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233331
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233193
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233191
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180822
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233339
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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