TY - JOUR
T1 - A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer
T2 - A trial of the ECOG-ACRIN Cancer Research Group (E2511)
AU - Owonikoko, Taofeek K.
AU - Dahlberg, Suzanne E.
AU - Khan, Saad A.
AU - Gerber, David E.
AU - Dowell, Jonathan
AU - Moss, Rebecca A.
AU - Belani, Chandra P.
AU - Hann, Christine L.
AU - Aggarwal, Charu
AU - Ramalingam, Suresh S.
N1 - Funding Information:
This study was conducted by the ECOG–ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820 , CA180794 , CA180864 , CA180870 , CA180802 , and from the National Cancer Institute , National Institutes of Health and the Department of Health and Human Services . Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. T.K. Owonikoko was supported by NIH/NCI grant 5K23CA164015 .
Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.lungcan.2015.04.015
DO - 10.1016/j.lungcan.2015.04.015
M3 - Article
C2 - 25985977
AN - SCOPUS:84931578364
SN - 0169-5002
VL - 89
SP - 66
EP - 70
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -
