A Phase I/II Study of Veliparib (ABT-888) in Combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Michael J PishvaianJonathan R Brody

Abstract

Up to 17% of patients with pancreatic ductal adenocarcinoma (PDAC) harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as BRCA1/2, or PALB2. Platinum-based chemotherapy, or treatment with PARP inhibitors are of particular benefit in these patients. However, there may be even greater benefit when platinums and PARP inhibitors are combined. We performed a single-arm, open-label, phase I/II study of the PARP inhibitor, veliparib, with 5-fluorouracil (no 5FU bolus) and oxaliplatin (FOLFOX) for patients with metastatic PDAC. Thirty-one patients were enrolled in a phase I dose escalation of veliparib (40 mg to 250 mg twice a day, days 1-7 of each 14-day cycle), to identify the recommended phase II dose (RP2D) of veliparib for the combination. Another 33 patients were enrolled in two parallel phase II trials to assess the objective response rate (ORR) in untreated or in previously treated patients. If available, germline or somatic testing was collected to identify pathogenic HR-DDR mutations. The combination of veliparib and FOLFOX was tolerable at a RP2D of veliparib of 200 mg twice a day. The primary endpoint for both phase II cohorts was met, and the O...Continue Reading

References

Mar 1, 1989·Controlled Clinical Trials·R Simon
Jun 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H A BurrisD D Von Hoff
Aug 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A de GramontA Bonetti
May 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cherrie K DonawhoDavid J Frost
Feb 8, 2008·Nature Reviews. Cancer·Thomas HelledayRicky A Sharma
Jul 23, 2008·Current Opinion in Pharmacology·Christopher J Lord, Alan Ashworth
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Apr 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shivaani KummarJames H Doroshow
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
Mar 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arun RajanGiuseppe Giaccone
Oct 18, 2013·The New England Journal of Medicine·Daniel D Von HoffMarkus F Renschler
Nov 6, 2013·Cancer Research·Jamin D SteffenJohn M Pascal
Nov 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bella KaufmanSusan M Domchek
Mar 12, 2015·The Journal of Pharmacology and Experimental Therapeutics·Yuqiao ShenBing Wang
Oct 29, 2015·The New England Journal of Medicine·Joaquin MateoJohann S de Bono
Nov 23, 2015·Molecular Cell·Mark J O'Connor
Feb 26, 2016·Nature·Peter BaileySean M Grimmond
Jul 30, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maeve A LoweryEileen M O'Reilly
Aug 9, 2017·Journal of the National Comprehensive Cancer Network : JNCCN·Talia Golan, Milind Javle
Aug 10, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mallika S DhawanPamela N Munster
Jun 30, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael J PishvaianEmanuel F Petricoin
Jun 4, 2019·The New England Journal of Medicine·Talia GolanHedy L Kindler
Sep 29, 2019·The New England Journal of Medicine·Robert L ColemanMichael A Bookman
Jan 25, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eileen M O'ReillyDavid P Kelsen

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Citations

Dec 21, 2020·Genes, Chromosomes & Cancer·Hans Martin SinghChristoph Springfeld
Jan 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chinmayee Sethy, Chanakya Nath Kundu
Apr 22, 2021·DNA Repair·Parnia Rahnamay FarnoodBahman Yousefi
May 25, 2021·Therapeutic Advances in Gastroenterology·Jeffrey ChiMuhammad Wasif Saif
Jul 10, 2021·Signal Transduction and Targeted Therapy·Ruixue Huang, Ping-Kun Zhou
Aug 17, 2021·Pancreas·Andrew TrunkIgnacio Garrido-Laguna
Aug 18, 2021·Cancer Metastasis Reviews·Fionnuala CrowleyEileen M O'Reilly
Aug 28, 2021·Biomedicines·Abdullah AlhusainiNiamh Lynam-Lennon
Oct 30, 2021·Frontiers in Cell and Developmental Biology·Jojanneke StoofNaomi Walsh
Nov 4, 2021·Expert Opinion on Investigational Drugs·Byung Woog Kang, Ian Chau

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