A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511)

Taofeek K. Owonikoko, Suzanne E. Dahlberg, Saad A. Khan, David E. Gerber, Jonathan Dowell, Rebecca A. Moss, Chandra P. Belani, Christine L. Hann, Charu Aggarwal, Suresh S. Ramalingam

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Objectives: Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to establish the safety of the combination in human subjects. Materials and methods: The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75mg/m2 on day 1) and E (100mg/m2 on days 1-3) in a 21-day cycle. The starting dose of V was 60mg (bid days 1-7) with plan to escalate to 100mg (days 1-7) or de-escalate to 40mg (days 1-7) depending on the dose limiting toxicity (DLT) experience during cycle 1. Patients with treatment-naïve, extensive stage SCLC were included. Results: The study enrolled 9 patients: M/F (4/5); median age (60); White/African American (8/1). V was tolerated at the 60. mg (DLT in 0 of 3 patients) and 100. mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100. mg in combination with standard doses of C and E was established as the RP2D. Grades 3-5 adverse events irrespective of attribution during cycle 1 included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1), heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8), respiratory failure (1), and thrombocytopenia (2). Investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial response in 4/7 (57.1%), and complete response in 1/7 (14.3%) patients. Conclusions: This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients.

Original languageEnglish (US)
Pages (from-to)66-70
Number of pages5
JournalLung Cancer
Volume89
Issue number1
DOIs
StatePublished - Jul 1 2015

Keywords

  • PARP
  • Phase I
  • Small cell
  • Veliparib

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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