Trial Outcomes & Findings for Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer (NCT NCT01657799)

Last Updated: 2018-06-06

Results Overview

Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

307 participants

Primary outcome timeframe

From randomization up to 36 months

Results posted on

2018-06-06

Participant Flow

Participants were enrolled across 87 sites in Argentina, Australia, Belgium, Canada, Chile, Czech Republic, Egypt, Finland, France, Hungary, Korea, Norway, Russia, Spain, Taiwan, Ukraine, and the United States.

Subjects were randomized in a 1:1:1 ratio to one of three treatment groups. Randomization was stratified by graded prognostic assessment (GPA) score (≤ 2.5 versus \> 2.5) and neurological symptoms (symptomatic versus asymptomatic).

Participant milestones

Participant milestones
Measure	Placebo BID + WBRT Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Overall Study STARTED	102	103	102
Overall Study Received Treatment	101	103	102
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	102	103	102

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo BID + WBRT Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Overall Study Adverse Event Related to progression	6	8	12
Overall Study Adverse Event Not Related to Progression	5	4	4
Overall Study Withdrawal by Subject	13	10	10
Overall Study Lost to Follow-up	1	0	1
Overall Study Disease Progression	2	4	4
Overall Study Progressive Disease Clinical	7	4	7
Overall Study Radiographic & Clinical Progression	16	11	15
Overall Study Other	52	62	49

Baseline Characteristics

Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo BID + WBRT n=102 Participants Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 Participants Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 Participants Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Total n=307 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 9.71 • n=5 Participants	59.8 years STANDARD_DEVIATION 8.74 • n=7 Participants	61.8 years STANDARD_DEVIATION 9.08 • n=5 Participants	60.6 years STANDARD_DEVIATION 9.20 • n=4 Participants
Age, Customized < 65 years	68 Participants n=5 Participants	73 Participants n=7 Participants	64 Participants n=5 Participants	205 Participants n=4 Participants
Age, Customized ≥ 65 years	34 Participants n=5 Participants	30 Participants n=7 Participants	38 Participants n=5 Participants	102 Participants n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	42 Participants n=7 Participants	36 Participants n=5 Participants	124 Participants n=4 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	61 Participants n=7 Participants	66 Participants n=5 Participants	183 Participants n=4 Participants
Race/Ethnicity, Customized White	79 Participants n=5 Participants	85 Participants n=7 Participants	66 Participants n=5 Participants	230 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Asian	22 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants	66 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Multirace	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Graded Prognostic Assessment (GPA) ≤ 2.5	91 Participants n=5 Participants	91 Participants n=7 Participants	92 Participants n=5 Participants	274 Participants n=4 Participants
Graded Prognostic Assessment (GPA) > 2.5	11 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	33 Participants n=4 Participants

PRIMARY outcome

Timeframe: From randomization up to 36 months

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Placebo BID + WBRT n=102 Participants Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 Participants Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 Participants Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Overall Survival	185 days Interval 137.0 to 251.0	209 days Interval 169.0 to 264.0	209 days Interval 138.0 to 255.0

SECONDARY outcome

Timeframe: From randomization up to 24 months

Population: All randomized participants

Best tumor response rate was calculated as the percentage of participants with a complete response or partial response, as determined by brain scan imaging (magnetic resonance image or computed tomography) by a central imaging vendor. Response was assessed according to the modified bidimensional criteria: Complete response required all of the following: complete disappearance of all target and non-target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease; no systemic corticosteroid dose. Partial response required all of the following: ≥ 50% decrease compared with baseline in the size of all target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease and no unequivocal progression of non-target lesions, which, even in presence of stable disease or progressive disease in target lesions, was significant enough to qualify as progression; stable or reduced daily total systemic corticosteroid dose.

Outcome measures

Outcome measures
Measure	Placebo BID + WBRT n=102 Participants Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 Participants Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 Participants Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Best Tumor Response Rate	41.2 percentage of participants Interval 31.5 to 51.4	36.9 percentage of participants Interval 27.6 to 47.0	42.2 percentage of participants Interval 32.4 to 52.3

SECONDARY outcome

Timeframe: From randomization up to 24 months

Population: All randomized participants

Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the first intracranial progression, as determined by brain scan imaging (magnetic resonance image \[MRI\]/ computed tomography \[CT\] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the participant was still taking study treatment or had previously discontinued study treatment. If the participant did not have a confirmed event of intracranial progression, their data were censored at the date of the last available intracranial progression assessment. Time to intracranial progression (radiographic) was estimated for each treatment group using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Placebo BID + WBRT n=102 Participants Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 Participants Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 Participants Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Time to Intracranial Progression (Radiographic)	259 days Interval 184.0 to Could not be estimated due to the low number of events.	226 days Interval 147.0 to 360.0	224 days Interval 137.0 to 358.0

SECONDARY outcome

Timeframe: From randomization up to 24 months

Population: All randomized participants

Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the participant was still receiving study treatment or had previously discontinued study treatment. If a participant did not have an event of clinical brain metastases progression, their data were censored at the date of the last available clinical disease progression assessment. Time to clinical brain metastasis progression was estimated for each treatment group using Kaplan-Meier methodology.

Outcome measures

Outcome measures
Measure	Placebo BID + WBRT n=102 Participants Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 Participants Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 Participants Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Time to Clinical Brain Metastasis Progression	348 days Interval 216.0 to Could not be estimated due to the low number of events	286 days Interval 192.0 to Could not be estimated due to the low number of events	255 days Interval 204.0 to 342.0

Adverse Events

Placebo BID + WBRT

Serious events: 39 serious events

Other events: 78 other events

Deaths: 0 deaths

Veliparib 50 mg BID + WBRT

Serious events: 31 serious events

Other events: 76 other events

Deaths: 0 deaths

Veliparib 200 mg BID + WBRT

Serious events: 36 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo BID + WBRT n=101 participants at risk Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 50 mg BID + WBRT n=103 participants at risk Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.	Veliparib 200 mg BID + WBRT n=102 participants at risk Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
Blood and lymphatic system disorders THROMBOCYTOPENIA	2.0% 2/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	3.9% 4/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.9% 6/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Gastrointestinal disorders CONSTIPATION	10.9% 11/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	9.7% 10/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	10.8% 11/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Gastrointestinal disorders DIARRHOEA	7.9% 8/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	7.8% 8/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	6.9% 7/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Gastrointestinal disorders NAUSEA	28.7% 29/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	22.3% 23/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	31.4% 32/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Gastrointestinal disorders VOMITING	13.9% 14/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	4.9% 5/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	8.8% 9/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
General disorders ASTHENIA	10.9% 11/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	8.7% 9/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	12.7% 13/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
General disorders FATIGUE	19.8% 20/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	26.2% 27/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	20.6% 21/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
General disorders PYREXIA	6.9% 7/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	6.8% 7/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	3.9% 4/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Infections and infestations ORAL CANDIDIASIS	6.9% 7/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	2.9% 3/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	4.9% 5/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Injury, poisoning and procedural complications RADIATION SKIN INJURY	5.0% 5/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	4.9% 5/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.9% 6/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Metabolism and nutrition disorders DECREASED APPETITE	13.9% 14/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	10.7% 11/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	14.7% 15/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	5.9% 6/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	6.8% 7/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	3.9% 4/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Nervous system disorders DIZZINESS	10.9% 11/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	7.8% 8/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	9.8% 10/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Nervous system disorders DYSGEUSIA	6.9% 7/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	3.9% 4/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	2.0% 2/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Nervous system disorders HEADACHE	14.9% 15/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	17.5% 18/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	20.6% 21/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Psychiatric disorders ANXIETY	7.9% 8/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.8% 6/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	2.0% 2/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Psychiatric disorders INSOMNIA	10.9% 11/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	9.7% 10/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.9% 6/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Respiratory, thoracic and mediastinal disorders COUGH	5.9% 6/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.8% 6/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	2.0% 2/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	13.9% 14/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	6.8% 7/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	9.8% 10/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Skin and subcutaneous tissue disorders ALOPECIA	18.8% 19/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	14.6% 15/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	14.7% 15/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.
Skin and subcutaneous tissue disorders RASH	2.0% 2/101 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	5.8% 6/103 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.	6.9% 7/102 • From first dose of study drug until 30 days following last dose of study drug; median duration of treatment was 15 days.