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).

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 (75 mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle. The starting dose of V was 60 mg (bid days 1-7) with plan to escalate to 100mg (days 1-7) or de-escalate to 40 mg (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 100mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100mg 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.

• Authors: 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
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 89 Issue 1 Pg. 66-70 (Jul 2015) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 25985977 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Benzimidazoles
• veliparib
• Etoposide
• Cisplatin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Benzimidazoles (administration & dosage, adverse effects)
• Chemotherapy-Induced Febrile Neutropenia (etiology)
• Cisplatin (administration & dosage)
• Etoposide (administration & dosage)
• Fatigue (chemically induced)
• Female
• Heart Failure (chemically induced)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Small Cell Lung Carcinoma (drug therapy, pathology)
• Thrombocytopenia (chemically induced)