Trial Outcomes & Findings for Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer (NCT NCT01642251)

Last Updated: 2023-05-06

Results Overview

dose of veliparib which was deemed to be the recommended phase II dose to be administered in the combination with CE for the phase II clinical trial

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

156 participants

Primary outcome timeframe

assessed for a maximum of cycle 1

Results posted on

2023-05-06

Participant Flow

This study opened to accrual on 9/28/2012, was suspended to accrual on 7/23/2013 after nine patients had been enrolled to phase I portion of the trial (3 patients at dose level 1; 6 patients at dose level 2). Phase II portion of the trial was activated on 10/24/2013 and enrolled 147 patients prior to study accrual completion on 7/2/2015.

Participant milestones

Participant milestones
Measure	Phase I: Arm A (Dose Level 1) The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase I: Arm B (Dose Level II) The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm D (Veliparib) Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Veliparib: Given PO	Phase II: Arm E (Placebo) Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Overall Study Eligible	3	6	72	69
Overall Study Eligible and Treated	3	6	64	64
Overall Study COMPLETED	3	6	53	49
Overall Study NOT COMPLETED	0	0	22	23
Overall Study STARTED	3	6	75	72
Overall Study Started Protocol Therapy	3	6	66	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase II: Arm D (Veliparib) Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Veliparib: Given PO	Phase II: Arm E (Placebo) Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Overall Study Progressive disease	3	3
Overall Study Adverse Event	5	4
Overall Study Death	1	3
Overall Study Withdrawal by Subject	1	3
Overall Study Alternative therapy	0	2
Overall Study Other complicating disease	1	0
Overall Study Ineligible/never start protocol therapy	11	8

Baseline Characteristics

Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=9 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm D (Veliparib) n=64 Participants Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Veliparib: Given PO	Phase II: Arm E (Placebo) n=64 Participants Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib	Total n=137 Participants Total of all reporting groups
Age, Continuous	60 years n=5 Participants	66 years n=7 Participants	64 years n=5 Participants	65 years n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	30 Participants n=7 Participants	32 Participants n=5 Participants	67 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	34 Participants n=7 Participants	32 Participants n=5 Participants	70 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	61 Participants n=7 Participants	57 Participants n=5 Participants	126 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: assessed for a maximum of cycle 1

Population: all eligible and treated patients

dose of veliparib which was deemed to be the recommended phase II dose to be administered in the combination with CE for the phase II clinical trial

Outcome measures

Outcome measures
Measure	Phase I n=9 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm E (Placebo) Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Recommended Phase II Dose (Phase I)	100 mg	—

PRIMARY outcome

Timeframe: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of first documented progression or death. No specific requirements if patient is > 3 years from registration

Population: Eligible and treated patients

Profession free survival (PFS) is defined as time from randomization to date of disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date they were last known to be alive and progression-free. Tumor response was evaluated via Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, and progression was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Median PFS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Phase I n=64 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm E (Placebo) n=64 Participants Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Progression Free Survival (Phase II) Overall sample	6.1 months Interval 5.9 to 6.2	5.5 months Interval 5.1 to 5.7
Progression Free Survival (Phase II) Patients within the male/abnormal LDH stratum	6.2 months Interval 5.9 to 7.5	5.1 months Interval 4.3 to 5.5
Progression Free Survival (Phase II) Patients not within the male/abnormal LDH stratum	6.0 months Interval 5.8 to 6.3	5.6 months Interval 5.3 to 6.3

SECONDARY outcome

Timeframe: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of death. No specific requirements if patient is > 3 years from registration

Population: Eligible and treated patients

Overall survival (OS) is defined as time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Phase I n=64 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm E (Placebo) n=64 Participants Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Overall Survival (OS)	10.3 months Interval 8.9 to 12.0	8.9 months Interval 8.3 to 11.3

SECONDARY outcome

Timeframe: assessed every 6 weeks while on study, then every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration.

Population: Eligible and treated patients

Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Complete response (CR) was defined as disappearance of all target lesions. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall response rate= (CR+PR)/all eligible and treated patients

Outcome measures

Outcome measures
Measure	Phase I n=64 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm E (Placebo) n=64 Participants Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Overall Response Rate (ORR)	72 percentage of patients Interval 59.0 to 82.0	66 percentage of patients Interval 53.0 to 77.0

OTHER_PRE_SPECIFIED outcome

Timeframe: assessed at baseline and 3 months after treatment initiation

Population: eligible and treated patients who had neurotoxicity data at both baseline and 3 months assessments

Neurotoxicity total score was measured by the 11 items in the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. Each item was scored from 0-4. The severity of neurotoxicity was measured by the total score of the 11 items, ranged from 0 to 44. Lower values of the FACT/GOG-Ntx neurotoxicity total score indicate higher neurotoxicity.

Outcome measures

Outcome measures
Measure	Phase I n=58 Participants The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm E (Placebo) n=45 Participants Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Neurotoxicity Total Score Change Between Baseline and 3 Months After Treatment Start	-0.1 units on a scale Standard Deviation 4.8	-1.8 units on a scale Standard Deviation 6.4

Adverse Events

Phase I: Arm A (Dose Level 1)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase I: Arm B (Dose Level 2)

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II: Arm D (Veliparib)

Serious events: 47 serious events

Other events: 63 other events

Deaths: 51 deaths

Phase II: Arm E (Placebo)

Serious events: 40 serious events

Other events: 62 other events

Deaths: 54 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Cancer Research Group

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Phase I: Arm A (Dose Level 1) n=3 participants at risk The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase I: Arm B (Dose Level 2) n=6 participants at risk The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm D (Veliparib) n=66 participants at risk Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Veliparib: Given PO	Phase II: Arm E (Placebo) n=66 participants at risk Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	18.2% 12/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	12.1% 8/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Cardiac disorders Atrial flutter	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Cardiac disorders Heart failure	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Death NOS	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Fatigue	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	33.3% 2/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Fever	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Nausea	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	50.0% 3/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Vomiting	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Infections and infestations Duodenal infection	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations CD4 lymphocytes decreased	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	6.1% 4/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Lymphocyte count decreased	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Neutrophil count decreased	66.7% 2/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	100.0% 6/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	31.8% 21/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	21.2% 14/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Platelet count decreased	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	33.3% 2/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Weight loss	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations White blood cell decreased	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	83.3% 5/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	4.5% 3/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Nervous system disorders Dizziness	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Vascular disorders Hypertension	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment

Measure	Phase I: Arm A (Dose Level 1) n=3 participants at risk The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase I: Arm B (Dose Level 2) n=6 participants at risk The phase I portion of the study was designed to determine the recommended dose for veliparib for the phase II portion of the trial. A total of 9 patients were treated on the phase I study. A total of 3 dose levels of veliparib were planned: 60mg (level 1), 100gm (level 2) and 40mg (level -1). 1 cycle=3 weeks, maximum of 4 cycles.	Phase II: Arm D (Veliparib) n=66 participants at risk Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Veliparib: Given PO	Phase II: Arm E (Placebo) n=66 participants at risk Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Etoposide: Given IV Placebo: placebo of Veliparib
Ear and labyrinth disorders Tinnitus	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	100.0% 6/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	18.2% 12/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	24.2% 16/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Chills	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Fatigue	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	83.3% 5/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	4.5% 3/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Fever	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
General disorders Infusion related reaction	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	66.7% 4/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	63.6% 42/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	53.0% 35/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Skin hyperpigmentation	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	4.5% 3/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	9.1% 6/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Constipation	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	50.0% 3/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	4.5% 3/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Nausea	100.0% 3/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	66.7% 4/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	3.0% 2/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Vomiting	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	50.0% 3/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Lymphocyte count decreased	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Neutrophil count decreased	100.0% 3/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	33.3% 2/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	1.5% 1/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Platelet count decreased	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	83.3% 5/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations White blood cell decreased	100.0% 3/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	50.0% 3/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Investigations Investigations - Other, specify	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	33.3% 1/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Nervous system disorders Dysgeusia	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	33.3% 2/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Nervous system disorders Headache	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Psychiatric disorders Depression	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment
Vascular disorders Flushing	0.00% 0/3 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	16.7% 1/6 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment	0.00% 0/66 • Assessed every cycle (1 cycle= 21 days) while on treatment and for 30 days after the end of treatment