A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer

• Sponsor: AbbVie (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02163694
• Collaborator: (none)
• Enrollment: 509
• Locations: 219
• Arms: 2
• Anticipated Duration (Months): 96.6
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin and paclitaxel (C/P) compared to placebo plus C/P in participants with a Breast Cancer Gene 1 or 2 (BRCA1; BRCA2) mutation in Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic or locally advanced unresectable breast cancer. The secondary objectives of the study are to assess overall survival (OS), clinical benefit rate (CBR) through the end of Week 24, objective response rate (ORR) and PFS on subsequent therapy (PFS2) in participants treated with veliparib in combination with C/P versus placebo in combination with C/P.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Veliparib Placebo; Drug: Veliparib; Drug: Carboplatin; Drug: Paclitaxel	Phase 3

Detailed Description

This is a Phase 3, randomized, double-blind, multinational, multicenter study to evaluate the efficacy and tolerability of veliparib in combination with C/P compared to placebo in combination with C/P in participants with a BRCA1 or BRCA2 mutation, as documented by the Sponsor core laboratory, with HER2-negative metastatic or locally advanced unresectable breast cancer who received no more than 2 prior lines of cytotoxic therapy for metastatic disease. For the purposes of eligibility, HER2-negative status was based on the most recent tumor biopsy. Participants were randomized in a 2:1 ratio, with a total of approximately 500 participants planned to be randomized. Veliparib 120 mg/placebo twice a day (BID) was dosed Days -2 through 5 with carboplatin target area under the concentration-time curve (AUC) 6 administered on Day 1 and paclitaxel 80 mg/m2 administered weekly on Days 1, 8, and 15 of each 21-day cycle.

Safety and efficacy data through the prespecified primary analysis cutoff date of 05 April 2019 are included in the interim analysis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 509 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer
• Actual Study Start Date: Jul 17, 2014
• Actual Primary Completion Date: Apr 5, 2019
• Anticipated Study Completion Date: Aug 5, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Veliparib Placebo with Carboplatin and Paclitaxel Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Drug: Veliparib Placebo; Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.; Drug: Carboplatin; Administered intravenously over approximately 15 to 30 minutes at an area under the curve (AUC) of 6 mg/mL/min immediately following paclitaxel infusion on Day 1 of every cycle. The duration of carboplatin infusion may be lengthened according to institutional guidelines.; Drug: Paclitaxel; Administered by intravenous infusion over approximately 1 hour at a dose of 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel is to be infused prior to carboplatin on Day 1. Dosing of veliparib/placebo is to be completed before the carboplatin or paclitaxel infusions.
Experimental: Veliparib with Carboplatin and Paclitaxel Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Drug: Veliparib; Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.; Other Names: ABT-888 ; Drug: Carboplatin; Administered intravenously over approximately 15 to 30 minutes at an area under the curve (AUC) of 6 mg/mL/min immediately following paclitaxel infusion on Day 1 of every cycle. The duration of carboplatin infusion may be lengthened according to institutional guidelines.; Drug: Paclitaxel; Administered by intravenous infusion over approximately 1 hour at a dose of 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel is to be infused prior to carboplatin on Day 1. Dosing of veliparib/placebo is to be completed before the carboplatin or paclitaxel infusions.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From randomization until the primary analysis data cut-off date of 05 April 2019; the median duration of follow-up was 35.5 months]

   Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology.

Secondary Outcome Measures

1. Overall Survival (OS) [Approximately 8 years from randomization]

   Time to death (overall survival) is defined as the number of days from the date the participant was randomized to the date of the participant's death. All events of death which occur up to the analysis cutoff date are to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant has not died, the data for the participant is to be censored at the date last known to be alive or at the analysis cutoff date if that is earlier. The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT population.

2. Clinical Benefit Rate (CBR) [Through the end of Week 24]

   The clinical benefit rate (CBR) for each treatment group was to be obtained from a time-to-event analysis of radiographic disease progression per the investigator. CBR is defined as the progression-free rate at 24 weeks (168 days), estimated for each treatment arm using Kaplan Meier methodology. All events of disease progression in the primary progression free survival analysis database were to be included, regardless of whether the event occurred while the participant was still taking, or had previously discontinued, study drug. If the participant had not yet progressed then their data was to be censored at the date of the last evaluable disease progression assessment. Participants without post-baseline assessments were to be censored at the date of randomization. The final analysis of CBR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.

3. Objective Response Rate (ORR) [Approximately 8 years from randomization]

   The objective response rate (ORR) is calculated as the percentage of participants who have a confirmed partial response (PR) or complete response (CR) based on assessment by the investigators per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. All participants who had at least one measurable lesion at baseline were to be included in the ORR calculation. The final analysis of ORR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.

4. Progression-Free Survival on Subsequent Therapy (PFS2) [Approximately 8 years from randomization]

   PFS2 is defined as the number of days from the date of randomization to the time of disease progression on subsequent therapy or death from any cause. The distribution of PFS2 was to be estimated for each treatment group using Kaplan-Meier methodology. The final analysis of PFS2 will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent.

2. Suspected deleterious or deleterious Breast Cancer Gene 1 (BRCA1) and/or Breast Cancer Gene 2 (BRCA2) germline mutation.

3. Breast cancer must be Human Epidermal Growth Factor Receptor 2 (HER2)-negative.

4. Measurable or non-measurable (but radiologically evaluable) disease per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1 on computed tomography (CT) scan (within 28 days of randomization) with at least one lesion outside previously irradiated areas.

5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.

6. Adequate hematologic, renal, and hepatic function (within 28 days of randomization).

Exclusion Criteria:

1. More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.

• Regimens received in the adjuvant/neoadjuvant setting or for locally advanced breast cancer within the past 6 months will also be considered toward the maximum of 2 prior lines of therapy. Adjuvant/neoadjuvant chemotherapy for one cancer event will count as one prior line of therapy, if received within the past 6 months.

• Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab) are allowed and are not counted towards the prior line of therapy.

1. Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant, neoadjuvant, or metastatic).

2. Prior therapy with Poly(ADP-ribose)-Polymerase (PARP) inhibitors.

3. Prior taxane therapy administered for the treatment of metastatic breast cancer with the below exceptions.

• Prior taxane therapy for metastatic breast cancer is allowed if the patient received ≤ 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to Cycle 1 Day-2 (C1D-2).

• Use of taxanes as adjuvant therapy or to treat locally advanced disease is permitted, if given more than 6 months prior to C1D-2

1. Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.

2. Active CNS metastases or leptomeningeal disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Ctr /ID# 125011	Gilbert	Arizona	United States	85234
2	University of Arkansas for Medical Sciences /ID# 124992	Little Rock	Arkansas	United States	72205
3	City of Hope /ID# 127117	Duarte	California	United States	91010
4	California Cancer Associates for Research & Excellence (cCARE) /ID# 136078	Fresno	California	United States	93720
5	Moores Cancer Center at UC San Diego /ID# 124991	La Jolla	California	United States	92093
6	Hematology and Oncology Assoc /ID# 130058	Newport Beach	California	United States	92663
7	Cancer Research Collaboration /ID# 128860	Santa Ana	California	United States	92705
8	Icri /Id# 128520	Whittier	California	United States	90603
9	Univ of Colorado Cancer Center /ID# 124983	Aurora	Colorado	United States	80045
10	Saint Joseph Hospital /ID# 131768	Denver	Colorado	United States	80218
11	Norwalk Hospital /ID# 133509	Norwalk	Connecticut	United States	06856
12	Lynn Cancer Institute, Boca /ID# 125013	Boca Raton	Florida	United States	33486
13	Holy Cross Hospital /ID# 125012	Fort Lauderdale	Florida	United States	33308
14	Sacred Heart Hospital /ID# 128279	Pensacola	Florida	United States	32504
15	Moffitt Cancer Center /ID# 124990	Tampa	Florida	United States	33612-9416
16	Florida Cancer Specialists - East /ID# 125007	West Palm Beach	Florida	United States	33401
17	Emory Midtown Infectious Disease Clinic /ID# 133192	Atlanta	Georgia	United States	30322
18	The Cancer Ctr at DeKalb Med C /ID# 125024	Decatur	Georgia	United States	30033
19	University of Illinois - Chicago /ID# 127576	Chicago	Illinois	United States	60607
20	NorthShore University HealthSystem /ID# 124996	Evanston	Illinois	United States	60201
21	Midwestern Regional CTC /ID# 124986	Zion	Illinois	United States	60099
22	McFarland Clinic, PC /ID# 129904	Ames	Iowa	United States	50010
23	Johns Hopkins University /ID# 125015	Baltimore	Maryland	United States	21287
24	Baystate Medical Center /ID# 139461	Springfield	Massachusetts	United States	01199
25	UMass Chan Medical School /ID# 129067	Worcester	Massachusetts	United States	01655
26	Henry Ford Health System /ID# 134497	Detroit	Michigan	United States	48202
27	Spectrum Health Medical Group /ID# 133568	Grand Rapids	Michigan	United States	49503
28	Spectrum Health Medical Group /ID# 148471	Grand Rapids	Michigan	United States	49503
29	William Beaumont Hospital /ID# 125019	Royal Oak	Michigan	United States	48073-6710
30	Univ of Mississippi Med Ctr,US /ID# 131352	Jackson	Mississippi	United States	39216-4643
31	St. Lukes Cancer Institute /ID# 125023	Kansas City	Missouri	United States	64111-5905
32	Washington University-School of Medicine /ID# 127575	Saint Louis	Missouri	United States	63110
33	Nebraska Hematology Oncology /ID# 132711	Lincoln	Nebraska	United States	68506
34	Rutgers Cancer Institute of New Jersey /ID# 125017	New Brunswick	New Jersey	United States	08901
35	University of New Mexico /ID# 125349	Albuquerque	New Mexico	United States	87102-4517
36	Beth Israel Medical Center /ID# 125001	New York	New York	United States	10003
37	Mount Sinai St. Luke's /ID# 125003	New York	New York	United States	10025
38	Mission Cancer Center /ID# 134248	Asheville	North Carolina	United States	28801
39	Duke Cancer Center /ID# 124999	Durham	North Carolina	United States	27710-3000
40	The Ohio State University /ID# 125022	Columbus	Ohio	United States	43210
41	University of Toledo /ID# 134849	Toledo	Ohio	United States	43614
42	Oregon Health and Science University /ID# 134229	Portland	Oregon	United States	97239
43	Lehigh Valley Health Network /ID# 130059	Allentown	Pennsylvania	United States	18103
44	Lehigh Valley Hosp/Muhlenberg /ID# 130277	Bethlehem	Pennsylvania	United States	18017
45	Penn State University and Milton S. Hershey Medical Center /ID# 124997	Hershey	Pennsylvania	United States	17033
46	Allegheny General Hospital /ID# 135094	Pittsburgh	Pennsylvania	United States	15212
47	University of Pittsburgh MC /ID# 125005	Pittsburgh	Pennsylvania	United States	15260
48	Texas Health Physicians Group /ID# 137740	Arlington	Texas	United States	76012
49	University of Texas Southwestern Medical Center /ID# 124989	Dallas	Texas	United States	75390-7208
50	University of Texas MD Anderson Cancer Center /ID# 125353	Houston	Texas	United States	77030
51	University of Vermont Medical Center /ID# 125350	Burlington	Vermont	United States	05401-1473
52	Swedish Cancer Institute - Issaquah /ID# 131534	Issaquah	Washington	United States	98029-6201
53	Swedish Cancer Institute - Edmonds /ID# 131549	Seattle	Washington	United States	98104
54	Swedish Medical Center /ID# 125021	Seattle	Washington	United States	98104
55	Swedish Cancer Insititute - Ballard /ID# 131548	Seattle	Washington	United States	98107-3932
56	Northwest Medical Specialties - Tacoma /ID# 125344	Tacoma	Washington	United States	98405
57	COIBA Centro de Oncologia e Investigacion de Buenos Aires /ID# 124839	Berazategui	Buenos Aires	Argentina	1884
58	Clinica Pergamino /ID# 127158	Pergamino	Buenos Aires	Argentina	2700
59	Instituto de Oncoloia de Rosario /ID# 127157	Rosario	Santa Fe	Argentina	2000
60	Centro Oncologico Riojano Integral /ID# 127938	La Rioja		Argentina	5300
61	St George Hospital /ID# 129416	Kogarah	New South Wales	Australia	2217
62	Duplicate_The Prince of Wales Hospital /ID# 124845	Randwick	New South Wales	Australia	2031
63	Southern Medical Day Care Centre /ID# 124844	Wollongong	New South Wales	Australia	2500
64	Townsville University Hospital /ID# 126731	Douglas	Queensland	Australia	4814
65	Duplicate_Flinders Centre for Innovation /ID# 127535	Bedford Park	South Australia	Australia	5042
66	Royal Hobart Hospital /ID# 124849	Hobart	Tasmania	Australia	7000
67	The Royal Melbourne Hospital /ID# 124846	Parkville	Victoria	Australia	3050
68	Hollywood Private Hospital /ID# 124843	Nedlands	Western Australia	Australia	6009
69	Ordensklinikum Linz GmbH Elisabethinen /ID# 126185	Linz	Oberoesterreich	Austria	4010
70	Medizinische Universitaet Graz /ID# 126450	Graz	Steiermark	Austria	8036
71	Medizinische Universitaet Wien /ID# 126184	Vienna	Wien	Austria	1090
72	Landeskrankenhaus Salzburg-Universitätsklinikum der PMU (LKH) /ID# 126449	Salzburg		Austria	5020
73	Bobruysk Interdistrict Onco. /ID# 137729	Bobruisk		Belarus	213825
74	State Institution Republican Scientific Practical Center of Oncology and Medical /ID# 125223	Minsk		Belarus	223040
75	Duplicate_Mogilev Reg Clin Oncology Dis /ID# 137728	Mogilev		Belarus	212018
76	Vitebsk Regional Clinical Oncology Dispensary /ID# 125219	Vitebsk		Belarus	210603
77	Universitair Ziekenhuis Antwerpen /ID# 124977	Edegem	Antwerpen	Belgium	2650
78	UCL Saint-Luc /ID# 124976	Woluwe-Saint-Lambert	Bruxelles-Capitale	Belgium	1200
79	Grand Hôpital de Charleroi /ID# 124981	Charleroi	Hainaut	Belgium	6000
80	Universitair Ziekenhuis Leuven /ID# 124980	Leuven	Vlaams-Brabant	Belgium	3000
81	Duplicate_AZ St-Jan Brugge-Oostende AV /ID# 124975	Brugge	West-Vlaanderen	Belgium	8000
82	ZNA Middelheim /ID# 124978	Antwerp		Belgium	2020
83	CHU UCL Namur - Sainte Elisabeth /ID# 124979	Namur		Belgium	5000
84	Duplicate_Sunnybrook Health Sciences Ctr /ID# 124882	Toronto	Ontario	Canada	M4N 3M5
85	Duplicate_Jewish General Hospital /ID# 124880	Montreal	Quebec	Canada	H3T 1E2
86	CHUM - Notre-Dame Hospital /ID# 124879	Montréal	Quebec	Canada	H2X 0A9
87	Duplicate_CHUQ-Hospital St. Sacrement /ID# 124881	Quebec City	Quebec	Canada	G1S 4L8
88	Hospital Clinico Vina del Mar /ID# 130100	Vina Del Mar	Valparaíso	Chile	2520612
89	Hospital Clinico Vina del Mar /ID# 148502	Vina Del Mar	Valparaíso	Chile	2520612
90	Instituto Nacional del Cancer /ID# 129343	Santiago		Chile	8380455
91	ICOS - Inst Clinic Oncology /ID# 125236	Temuco		Chile	4810469
92	Hospital Pablo Tobon Uribe /ID# 126657	Medellín	Antioquia	Colombia	50034
93	Instituto Medico de Alta Tecnologia Oncomédica S.A /ID# 129211	Monteria	Cordoba	Colombia	230002
94	Administradora del Country_S.A-Clinica Del Country /ID# 125255	Bogota	Cundinamarca	Colombia	110221
95	Hospital Univ San Ignacio /ID# 126655	Bogota	Cundinamarca	Colombia	110231
96	Centro Medico Imbanaco de Cali /ID# 126656	Cali		Colombia
97	Fakultni Nemocnice Brno /ID# 128176	Brno		Czechia	625 00
98	Masarykuv onkologicky ustav /ID# 124886	Brno		Czechia	656 53
99	Duplicate_FN Hradec Kralove /ID# 127080	Hradec Kralove		Czechia	500 05
100	Fakultni nemocnice Olomouc /ID# 124885	Olomouc		Czechia	779 00
101	Vseobecna fakultni nemocnice v Praze /ID# 124887	Praha		Czechia	128 08
102	Rigshospitalet /ID# 124891	Copenhagen Ø	Hovedstaden	Denmark	2100
103	Sygehus Lillebælt, Vejle /ID# 124892	Vejle	Syddanmark	Denmark	7100
104	East Tallinn Central Hospital /ID# 126475	Kesklinna Linnaosa	Harjumaa	Estonia	10138
105	Docrates Cancer Center /ID# 124896	Helsinki		Finland	00180
106	Duplicate_Helsinki Univ Central Hospital /ID# 124897	Helsinki		Finland	00290
107	Duplicate_Tampere University Hospital /ID# 124898	Tampere		Finland	33521
108	Vaasa Central Hospital /ID# 132548	Vaasa		Finland	65130
109	Institut Paoli-Calmettes /ID# 124903	Marseille	Bouches-du-Rhone	France	13009
110	Institut Curie /ID# 124902	Paris CEDEX 05	Ile-de-France	France	75248
111	Institut de Cancérologie de l'Ouest René Gauducheau /ID# 137726	St Herblain CEDEX	Loire-Atlantique	France	44805
112	Institut Curie - site CLCC René Huguenin /ID# 124904	Saint-cloud		France	92210
113	Universitaetsklinik Heidelberg /ID# 126664	Heidelberg	Baden-Wuerttemberg	Germany	69120
114	Universitaetsklinimum Tuebingen /ID# 129968	Tubingen	Baden-Wuerttemberg	Germany	72076
115	Universitaetsklinikum Ulm /ID# 135230	Ulm	Baden-Wuerttemberg	Germany	89081
116	Universitaetsklinikum Koeln /ID# 126905	Köln	Nordrhein-Westfalen	Germany	50937
117	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 127180	Dresden		Germany	01307
118	Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 125256	Munich		Germany	81675
119	Sana Klinikum Offenbach /ID# 126733	Offenbach am Main		Germany	63069
120	Semmelweis Egyetem /ID# 132485	Budapest		Hungary	1085
121	Pecsi Tudomanyegyetem Klinikai Kozpont /ID# 125259	Pecs		Hungary	7624
122	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 124911	Szolnok		Hungary	5000
123	Duplicate_Zala Megyei Korhaz /ID# 131341	Zalaegerszeg		Hungary	8900
124	The Chaim Sheba Medical Center /ID# 124918	Ramat Gan	Tel-Aviv	Israel	5265601
125	Tel Aviv Sourasky Medical Center /ID# 130276	Tel Aviv-Yafo	Tel-Aviv	Israel	6423906
126	Duplicate_Soroka University Medical Center /ID# 124917	Be'er Sheva		Israel	8457101
127	Assaf Harofeh Medical Center /ID# 124915	Be'Er Ya'Akov		Israel	70300
128	Rambam Health Care Campus /ID# 124916	Haifa		Israel	3109601
129	Shaare Zedek Medical Center /ID# 130275	Jerusalem		Israel	91031
130	Gastroenterology Institute, Division of Medicine /ID# 124919	Jerusalem		Israel	91120
131	Kaplan Medical Center /ID# 124914	Rehovot		Israel	7661041
132	Ospedale San Raffaele IRCCS /ID# 125261	Milan	Lombardia	Italy	20132
133	IEO -Istituto Europeo di Oncologia /ID# 125260	Milan	Milano	Italy	20141
134	IRCCS Ospedale Sacro Cuore Don Calabria /ID# 125262	Negrar	Verona	Italy	37024
135	Centro di Riferimento Oncologico /ID# 126738	Aviano		Italy	33081
136	Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 125263	Reggio Calabria		Italy	89124
137	National Cancer Center /ID# 125602	Goyang	Gyeonggido	Korea, Republic of	10408
138	Yonsei University Health System Severance Hospital /ID# 125599	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03722
139	Korea University Anam Hospital /ID# 128968	Seoul		Korea, Republic of	02841
140	Seoul National University Hospital /ID# 125600	Seoul		Korea, Republic of	03080
141	Asan Medical Center /ID# 125601	Seoul		Korea, Republic of	05505
142	Samsung Medical Center /ID# 125598	Seoul		Korea, Republic of	06351
143	Pauls Stradins Clinical University Hospital /ID# 125264	Riga		Latvia	1002
144	Riga East Clinical University Hospital /ID# 125265	Riga		Latvia	LV-1079
145	Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 125266	Kaunas		Lithuania	50161
146	National Cancer Institute /ID# 125267	Vilnius		Lithuania	08660
147	Centro de Estudios Clínicos Especializados /ID# 128680	Mérida	Yucatan	Mexico	97133
148	Centro Oncologico de Chihuahua /ID# 128679	Chihuahua		Mexico	31217
149	Instituto Nacional de Cancerología INCAN /ID# 128676	Ciudad de Mexico		Mexico	14080
150	Erasmus Medisch Centrum /ID# 124935	Rotterdam	Zuid-Holland	Netherlands	3015 GD
151	Universitair Medisch Centrum Groningen /ID# 129069	Groningen		Netherlands	9713 GZ
152	Maastricht Universitair Medisch Centrum /ID# 129068	Maastricht		Netherlands	6229 HX
153	Haukeland University Hospital /ID# 150177	Bergen	Hordaland	Norway	5021
154	Wojewodzki Szpital Specjalistyczny /ID# 127258	Wroclaw	Dolnoslaskie	Poland	51-124
155	Centrum Onkologii Lukaszczyka /ID# 124938	Bydgoszcz	Kujawsko-pomorskie	Poland	85-796
156	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 126999	Lodz	Lodzkie	Poland	93-513
157	MRUK-MED I Spolka z ograniczona odpowiedzialnoscia /ID# 124939	Rzeszow	Podkarpackie	Poland	35-021
158	Wojewodzki Szpital Zespolony /ID# 126998	Elblag	Warminsko-mazurskie	Poland	82-300
159	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE /ID# 126510	Vila Nova De Gaia	Porto	Portugal	4434-502
160	Centro Hospitalar Universitário do Algarve, EPE - Hospital Faro /ID# 125298	Faro		Portugal	8000-386
161	Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 125299	Lisboa		Portugal	1649-035
162	Unidade Local de Saúde de Matosinhos, EPE /ID# 126511	Matosinhos		Portugal	4464-513
163	IPO Porto FG, EPE /ID# 125297	Porto		Portugal	4200-072
164	Centro Hospitalar Universitario de Sao Joao, EPE /ID# 126508	Porto		Portugal	4200-319
165	Ad-Vance Medical Research, LLC /ID# 126043	Ponce		Puerto Rico	00717
166	San Juan Municipal Hospital /ID# 124695	San Juan		Puerto Rico	00935
167	S.C. Centrul de Oncologie Sf. Nectarie S.R.L. /ID# 124948	Craiova	Dolj	Romania	200347
168	Duplicate_lnstitutul Oncologic Prof Dr Alexandru Trestioreanu /ID# 124943	Bucharest		Romania	022328
169	Spitalul Clinic Judetean de Urgenta Cluj -Napoca /ID# 124945	Cluj-Napoca		Romania	400006
170	Oncomed SRL /ID# 127598	Timisoara		Romania	300239
171	Sverdlovsk Regional Oncology Dispensary /ID# 130950	Yekaterinburg	Sverdlovskaya Oblast	Russian Federation	620043
172	Regional Oncology Dispensary /ID# 125936	Kursk	Tatarstan, Respublika	Russian Federation	305035
173	Duplicate_archangel Clinical Oncology /ID# 126031	Arkhangelsk		Russian Federation	163045
174	Altay Regional Oncological Dispesary /ID# 127160	Barnaul		Russian Federation	656049
175	Belgorod Oncology Dispensary /ID# 129315	Belgorod		Russian Federation	308010
176	Duplicate_Saratov State Medical University n.s. Chernyshevskiy /ID# 139395	Saratov		Russian Federation	410012
177	LLC BioEq Ltd. /ID# 134529	St. Petersburg		Russian Federation	197342
178	Siberian State Medical University /ID# 127161	Tomsk		Russian Federation	634050
179	Volgograd Regional Clinical Oncology Dispensary /ID# 124952	Volzhsky		Russian Federation	404130
180	National University Hospital /ID# 125315	Singapore		Singapore	119074
181	Johns Hopkins Singapore IMC /ID# 125316	Singapore		Singapore	308433
182	GVI Oncology /ID# 125321	Gqeberha	Eastern Cape	South Africa	6006
183	University of Free State, Universitas Annex (National Hospital Grounds) /ID# 128499	Bloemfontein	Free State	South Africa	9301
184	Wits Clinical Research Site /ID# 125317	Johannesburg	Gauteng	South Africa	2193
185	Medical Oncology Ctr Rosebank /ID# 125322	Johannesburg	Gauteng	South Africa	2196
186	Sandton Oncology Medical Group PTY Ltd /ID# 125323	Johannesburg	Gauteng	South Africa	2196
187	Mary Potter Oncology Centre /ID# 133269	Pretoria	Gauteng	South Africa	0181
188	The Oncology Centre /ID# 126104	Durban	Kwazulu-Natal	South Africa	4091
189	Netcare Oncology Intervent Ctr /ID# 125320	Cape Town	Western Cape	South Africa	7460
190	Cancercare Outeniqua Oncology Centre /ID# 125319	George	Western Cape	South Africa	6530
191	Hospital Santa Creu i Sant Pau /ID# 124963	Barcelona		Spain	08041
192	Hospital General Universitario Gregorio Maranon /ID# 124962	Madrid		Spain	28007
193	Hospital Universitario HM Sanchinarro /ID# 124960	Madrid		Spain	28050
194	Hospital Universitario Virgen de la Victoria /ID# 124961	Malaga		Spain	29010
195	Hospital Clinico Universitario de Valencia /ID# 124959	Valencia		Spain	46010
196	Skane University hospital /ID# 124966	Malmo	Skane Lan	Sweden	214 28
197	Norrlands University hospital /ID# 124967	Umea	Vasterbottens Lan	Sweden	581 85
198	Sahlgrenska University Hospital /ID# 124965	Gothenburg	Vastra Gotalands Lan	Sweden	413 45
199	Linkoping University Hospital /ID# 126795	Linkoping		Sweden	581 85
200	Duplicate_Karolinska Univ Sjukhuset /ID# 124964	Solna		Sweden	171 64
201	Uppsala University Hospital /ID# 126512	Uppsala		Sweden	75185
202	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 125575	Kaohsiung		Taiwan	807
203	National Taiwan University Hospital /ID# 125324	Taipei City		Taiwan	100
204	Hacettepe University Faculty of Medicine /ID# 125336	Ankara		Turkey	06100
205	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 125337	Ankara		Turkey	06200
206	Duplicate_Akdeniz University Medical Fac /ID# 125339	Antalya		Turkey	07059
207	Bezmi Alem Univ Med Fac Hosp /ID# 127901	Istanbul		Turkey	34093
208	Istanbul University Istanbul Medical Faculty /ID# 145144	Istanbul		Turkey	34093
209	Municipal Non-Profit Enterprise City Clinical Hospital No.4 of Dnipro City Counc /ID# 124968	Dnipro		Ukraine	49102
210	Donetsk Regional Antitumor Ctr /ID# 124970	Donetsk		Ukraine	83092
211	Communal non-profit enterprise Regional Center of Oncology /ID# 124972	Kharkiv		Ukraine	61070
212	Lviv Oncological Regional Therapeutical and Diagnostic Centre /ID# 124974	Lviv		Ukraine	79031
213	Poltava Regional Clinical Oncology Centre of Poltava Regional Council /ID# 124969	Poltava		Ukraine	36011
214	Zaporizhzhia Med. Academy MOH /ID# 129800	Zaporizhia		Ukraine	69040
215	ME Kryviy Rih Oncology Dispensary /ID# 129806	Кривий Ріг		Ukraine	50048
216	University Hospitals Bristol /ID# 128343	Bristol	Bristol, City Of	United Kingdom	BS2 8ED
217	Hull University Teaching Hospitals NHS Trust /ID# 133030	Hull	East Riding Of Yorkshire	United Kingdom	HU3 2JZ
218	Nottingham University Hospitals NHS Trust /ID# 125340	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
219	University Hospitals Birmingham NHS Foundation Trust /ID# 125342	Birmingham		United Kingdom	B15 2TH

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

• Study Protocol - Jul 23, 2020
• Statistical Analysis Plan - May 30, 2019

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02163694
• Other Study ID Numbers: M12-914; 2014-000345-70
• First Posted: Jun 16, 2014
• Last Update Posted: Jun 14, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: PARP Inhibitor; Veliparib; BRCA1; BRCA2; HER2-negative; Locally recurrent; Breast Cancer; Metastatic Breast Cancer; ABT-888; Genetic breast cancer; Paclitaxel; BRCA Mutation; PARP; Carboplatin; BROCADE3
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Carboplatin; Veliparib

Study Results

Participant Flow

Pre-assignment Detail	ITT population: randomized participants who have been documented to have suspected deleterious or deleterious BRCA1/2 mutations by the sponsor core laboratory

Arm/Group Title	Veliparib Placebo With Carboplatin and Paclitaxel	Veliparib With Carboplatin and Paclitaxel
Arm/Group Description	Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.
Period Title: Overall Study
STARTED	172	337
COMPLETED	18	70
NOT COMPLETED	154	267

Baseline Characteristics

Arm/Group Title	Veliparib Placebo With Carboplatin and Paclitaxel	Veliparib With Carboplatin and Paclitaxel	Total
Arm/Group Description	Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Total of all reporting groups
Overall Participants	172	337	509
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (10.81)	46.8 (10.73)	46.8 (10.75)
Sex: Female, Male (Count of Participants)
Female	169 98.3%	333 98.8%	502 98.6%
Male	3 1.7%	4 1.2%	7 1.4%
Race/Ethnicity, Customized (Count of Participants)
White	153 89%	294 87.2%	447 87.8%
Black or African American	6 3.5%	14 4.2%	20 3.9%
Asian	12 7%	24 7.1%	36 7.1%
American Indian or Alaska Native	0 0%	3 0.9%	3 0.6%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%
Multiple	1 0.6%	2 0.6%	3 0.6%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology.
Time Frame	From randomization until the primary analysis data cut-off date of 05 April 2019; the median duration of follow-up was 35.5 months

Outcome Measure Data

Analysis Population Description

ITT population: randomized participants who have been documented to have suspected deleterious or deleterious BRCA1/2 mutations by the sponsor core laboratory

Arm/Group Title	Veliparib Placebo With Carboplatin and Paclitaxel	Veliparib With Carboplatin and Paclitaxel
Arm/Group Description	Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.	Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.
Measure Participants	172	337
Median (95% Confidence Interval) [months]	12.6	14.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Veliparib Placebo With Carboplatin and Paclitaxel, Veliparib With Carboplatin and Paclitaxel
	Comments	PFS was compared between the treatment groups using the log-rank test, stratified by prior platinum therapy (Yes versus No) and receptor status (estrogen receptor [ER] and/or progesterone receptor [PgR] positive versus ER/PgR negative).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Veliparib Placebo With Carboplatin and Paclitaxel, Veliparib With Carboplatin and Paclitaxel
	Comments	A Cox proportional hazards model, stratified by prior platinum therapy (Yes versus No) and receptor status (estrogen receptor (ER) and/or progesterone receptor (PgR) positive versus ER/PgR negative) was used to estimate the hazard ratio and 95% confidence interval comparing the two treatment arms.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard Ratio
	Estimated Value	0.705
	Confidence Interval	(2-Sided) 95%; 0.566 to 0.877
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Time to death (overall survival) is defined as the number of days from the date the participant was randomized to the date of the participant's death. All events of death which occur up to the analysis cutoff date are to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant has not died, the data for the participant is to be censored at the date last known to be alive or at the analysis cutoff date if that is earlier. The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT population.
Time Frame	Approximately 8 years from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	The clinical benefit rate (CBR) for each treatment group was to be obtained from a time-to-event analysis of radiographic disease progression per the investigator. CBR is defined as the progression-free rate at 24 weeks (168 days), estimated for each treatment arm using Kaplan Meier methodology. All events of disease progression in the primary progression free survival analysis database were to be included, regardless of whether the event occurred while the participant was still taking, or had previously discontinued, study drug. If the participant had not yet progressed then their data was to be censored at the date of the last evaluable disease progression assessment. Participants without post-baseline assessments were to be censored at the date of randomization. The final analysis of CBR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.
Time Frame	Through the end of Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	The objective response rate (ORR) is calculated as the percentage of participants who have a confirmed partial response (PR) or complete response (CR) based on assessment by the investigators per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. All participants who had at least one measurable lesion at baseline were to be included in the ORR calculation. The final analysis of ORR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.
Time Frame	Approximately 8 years from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Progression-Free Survival on Subsequent Therapy (PFS2)
Description	PFS2 is defined as the number of days from the date of randomization to the time of disease progression on subsequent therapy or death from any cause. The distribution of PFS2 was to be estimated for each treatment group using Kaplan-Meier methodology. The final analysis of PFS2 will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.
Time Frame	Approximately 8 years from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the first dose of study drug until 30 days after the last dose of any study treatment up to the data cut-off date of 05 April 2019; median duration of treatment with placebo for veliparib was 115 days (range: 2 to 1210 days) and median duration of treatment with veliparib was 117.5 days (range 2 to 1315 days)
Arm/Group Title	Veliparib Placebo With Carboplatin and Paclitaxel		Veliparib With Carboplatin and Paclitaxel
Arm/Group Description	Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.		Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle.
All Cause Mortality
	Veliparib Placebo With Carboplatin and Paclitaxel		Veliparib With Carboplatin and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/171 (52.6%)		171/336 (50.9%)
Serious Adverse Events
	Veliparib Placebo With Carboplatin and Paclitaxel		Veliparib With Carboplatin and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/171 (28.7%)		115/336 (34.2%)
Blood and lymphatic system disorders
ANAEMIA	5/171 (2.9%)	9	16/336 (4.8%)	21
FEBRILE NEUTROPENIA	3/171 (1.8%)	3	11/336 (3.3%)	11
HAEMORRHAGIC DISORDER	0/171 (0%)	0	1/336 (0.3%)	1
LEUKOPENIA	0/171 (0%)	0	2/336 (0.6%)	4
NEUTROPENIA	0/171 (0%)	0	8/336 (2.4%)	11
THROMBOCYTOPENIA	4/171 (2.3%)	5	14/336 (4.2%)	20
Cardiac disorders
CARDIOPULMONARY FAILURE	0/171 (0%)	0	1/336 (0.3%)	1
PERICARDITIS	0/171 (0%)	0	1/336 (0.3%)	3
Ear and labyrinth disorders
VERTIGO	0/171 (0%)	0	1/336 (0.3%)	1
Eye disorders
DIPLOPIA	0/171 (0%)	0	1/336 (0.3%)	1
RETINAL ARTERY OCCLUSION	0/171 (0%)	0	1/336 (0.3%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	0/171 (0%)	0	1/336 (0.3%)	1
ABDOMINAL PAIN LOWER	0/171 (0%)	0	1/336 (0.3%)	1
ABDOMINAL PAIN UPPER	1/171 (0.6%)	1	0/336 (0%)	0
COLITIS MICROSCOPIC	1/171 (0.6%)	1	0/336 (0%)	0
CONSTIPATION	0/171 (0%)	0	1/336 (0.3%)	2
DIARRHOEA	1/171 (0.6%)	1	2/336 (0.6%)	2
FAECALOMA	0/171 (0%)	0	1/336 (0.3%)	1
GASTRITIS	0/171 (0%)	0	1/336 (0.3%)	1
ILEUS	1/171 (0.6%)	1	0/336 (0%)	0
INTESTINAL OBSTRUCTION	0/171 (0%)	0	1/336 (0.3%)	2
NAUSEA	2/171 (1.2%)	2	6/336 (1.8%)	9
NONINFECTIVE SIALOADENITIS	0/171 (0%)	0	1/336 (0.3%)	1
PANCREATITIS ACUTE	0/171 (0%)	0	1/336 (0.3%)	1
SMALL INTESTINAL OBSTRUCTION	0/171 (0%)	0	1/336 (0.3%)	1
TOOTHACHE	0/171 (0%)	0	1/336 (0.3%)	1
VOMITING	1/171 (0.6%)	1	6/336 (1.8%)	8
General disorders
CHEST PAIN	0/171 (0%)	0	3/336 (0.9%)	3
FATIGUE	1/171 (0.6%)	1	2/336 (0.6%)	4
GENERAL PHYSICAL HEALTH DETERIORATION	1/171 (0.6%)	1	0/336 (0%)	0
MALAISE	0/171 (0%)	0	1/336 (0.3%)	1
NON-CARDIAC CHEST PAIN	0/171 (0%)	0	1/336 (0.3%)	1
PAIN	0/171 (0%)	0	1/336 (0.3%)	1
PYREXIA	4/171 (2.3%)	5	8/336 (2.4%)	11
Hepatobiliary disorders
CHOLECYSTITIS	0/171 (0%)	0	1/336 (0.3%)	1
CHOLELITHIASIS	0/171 (0%)	0	2/336 (0.6%)	2
Immune system disorders
ANAPHYLACTIC REACTION	0/171 (0%)	0	2/336 (0.6%)	2
CONTRAST MEDIA ALLERGY	1/171 (0.6%)	1	0/336 (0%)	0
DRUG HYPERSENSITIVITY	2/171 (1.2%)	2	1/336 (0.3%)	1
HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS	0/171 (0%)	0	1/336 (0.3%)	1
HYPERSENSITIVITY	1/171 (0.6%)	1	0/336 (0%)	0
Infections and infestations
ABSCESS JAW	0/171 (0%)	0	1/336 (0.3%)	1
APPENDICITIS	0/171 (0%)	0	2/336 (0.6%)	2
BREAST CELLULITIS	0/171 (0%)	0	1/336 (0.3%)	1
BRONCHITIS	0/171 (0%)	0	1/336 (0.3%)	1
CELLULITIS	0/171 (0%)	0	4/336 (1.2%)	5
DEVICE RELATED INFECTION	0/171 (0%)	0	2/336 (0.6%)	2
DEVICE RELATED SEPSIS	0/171 (0%)	0	1/336 (0.3%)	2
ERYSIPELAS	2/171 (1.2%)	2	2/336 (0.6%)	2
GASTROENTERITIS VIRAL	0/171 (0%)	0	1/336 (0.3%)	1
INFECTED DERMAL CYST	0/171 (0%)	0	1/336 (0.3%)	1
INFECTED LYMPHOCELE	0/171 (0%)	0	1/336 (0.3%)	1
INFECTION	2/171 (1.2%)	2	0/336 (0%)	0
INFLUENZA	1/171 (0.6%)	1	3/336 (0.9%)	3
LOWER RESPIRATORY TRACT INFECTION	0/171 (0%)	0	1/336 (0.3%)	1
LUNG INFECTION	1/171 (0.6%)	1	0/336 (0%)	0
MENINGITIS	1/171 (0.6%)	1	0/336 (0%)	0
MORAXELLA INFECTION	1/171 (0.6%)	1	0/336 (0%)	0
NASOPHARYNGITIS	0/171 (0%)	0	1/336 (0.3%)	1
NEUTROPENIC INFECTION	0/171 (0%)	0	2/336 (0.6%)	2
NEUTROPENIC SEPSIS	0/171 (0%)	0	1/336 (0.3%)	1
OPHTHALMIC HERPES ZOSTER	1/171 (0.6%)	1	0/336 (0%)	0
PAROTID ABSCESS	0/171 (0%)	0	1/336 (0.3%)	1
PNEUMOCYSTIS JIROVECII PNEUMONIA	0/171 (0%)	0	1/336 (0.3%)	2
PNEUMONIA	0/171 (0%)	0	7/336 (2.1%)	8
RESPIRATORY TRACT INFECTION	1/171 (0.6%)	1	0/336 (0%)	0
RESPIRATORY TRACT INFECTION VIRAL	0/171 (0%)	0	1/336 (0.3%)	1
SEPSIS	4/171 (2.3%)	4	4/336 (1.2%)	4
SEPTIC SHOCK	0/171 (0%)	0	1/336 (0.3%)	1
SINUSITIS	0/171 (0%)	0	3/336 (0.9%)	3
STAPHYLOCOCCAL SKIN INFECTION	1/171 (0.6%)	1	0/336 (0%)	0
UPPER RESPIRATORY TRACT INFECTION	0/171 (0%)	0	2/336 (0.6%)	3
URINARY TRACT INFECTION	0/171 (0%)	0	1/336 (0.3%)	1
UROSEPSIS	0/171 (0%)	0	1/336 (0.3%)	1
VASCULAR DEVICE INFECTION	2/171 (1.2%)	2	3/336 (0.9%)	3
VIRAL INFECTION	0/171 (0%)	0	1/336 (0.3%)	1
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE	0/171 (0%)	0	1/336 (0.3%)	1
PROCEDURAL PAIN	0/171 (0%)	0	1/336 (0.3%)	1
Metabolism and nutrition disorders
DEHYDRATION	1/171 (0.6%)	1	2/336 (0.6%)	2
DIABETES MELLITUS	1/171 (0.6%)	1	0/336 (0%)	0
ELECTROLYTE IMBALANCE	1/171 (0.6%)	1	0/336 (0%)	0
GOUT	1/171 (0.6%)	2	0/336 (0%)	0
HYPOKALAEMIA	0/171 (0%)	0	2/336 (0.6%)	2
Musculoskeletal and connective tissue disorders
BACK PAIN	0/171 (0%)	0	4/336 (1.2%)	4
INTERVERTEBRAL DISC PROTRUSION	0/171 (0%)	0	1/336 (0.3%)	1
MUSCULAR WEAKNESS	0/171 (0%)	0	1/336 (0.3%)	2
MUSCULOSKELETAL CHEST PAIN	0/171 (0%)	0	1/336 (0.3%)	1
NECK PAIN	0/171 (0%)	0	1/336 (0.3%)	1
OSTEOARTHRITIS	0/171 (0%)	0	1/336 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER METASTATIC	1/171 (0.6%)	1	0/336 (0%)	0
COLON CANCER	0/171 (0%)	0	1/336 (0.3%)	1
GASTRIC NEOPLASM	0/171 (0%)	0	1/336 (0.3%)	1
MALIGNANT NEOPLASM PROGRESSION	6/171 (3.5%)	6	13/336 (3.9%)	19
MALIGNANT PLEURAL EFFUSION	0/171 (0%)	0	1/336 (0.3%)	1
METASTASES TO CENTRAL NERVOUS SYSTEM	1/171 (0.6%)	1	0/336 (0%)	0
METASTASES TO MENINGES	1/171 (0.6%)	1	2/336 (0.6%)	2
MYELODYSPLASTIC SYNDROME	0/171 (0%)	0	1/336 (0.3%)	1
SECOND PRIMARY MALIGNANCY	0/171 (0%)	0	1/336 (0.3%)	1
TUMOUR PAIN	0/171 (0%)	0	1/336 (0.3%)	1
Nervous system disorders
APHASIA	0/171 (0%)	0	1/336 (0.3%)	1
BRAIN OEDEMA	0/171 (0%)	0	1/336 (0.3%)	1
CEREBRAL INFARCTION	0/171 (0%)	0	1/336 (0.3%)	1
DIZZINESS	1/171 (0.6%)	1	2/336 (0.6%)	2
DYSARTHRIA	0/171 (0%)	0	1/336 (0.3%)	1
HEADACHE	2/171 (1.2%)	2	0/336 (0%)	0
INTRACRANIAL PRESSURE INCREASED	1/171 (0.6%)	1	0/336 (0%)	0
LETHARGY	0/171 (0%)	0	1/336 (0.3%)	1
PRESYNCOPE	0/171 (0%)	0	1/336 (0.3%)	1
SCIATICA	1/171 (0.6%)	1	1/336 (0.3%)	1
SEIZURE	0/171 (0%)	0	3/336 (0.9%)	3
SYNCOPE	1/171 (0.6%)	1	0/336 (0%)	0
VASCULAR ENCEPHALOPATHY	1/171 (0.6%)	1	0/336 (0%)	0
Product Issues
DEVICE BREAKAGE	1/171 (0.6%)	1	0/336 (0%)	0
Psychiatric disorders
ANXIETY	1/171 (0.6%)	1	1/336 (0.3%)	1
MANIA	1/171 (0.6%)	1	0/336 (0%)	0
PSYCHOTIC DISORDER	0/171 (0%)	0	1/336 (0.3%)	1
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/171 (0.6%)	1	0/336 (0%)	0
CHRONIC KIDNEY DISEASE	0/171 (0%)	0	1/336 (0.3%)	1
HAEMATURIA	0/171 (0%)	0	1/336 (0.3%)	2
Reproductive system and breast disorders
PELVIC PAIN	0/171 (0%)	0	1/336 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
ATELECTASIS	1/171 (0.6%)	1	0/336 (0%)	0
DYSPNOEA	2/171 (1.2%)	2	2/336 (0.6%)	2
EPISTAXIS	0/171 (0%)	0	1/336 (0.3%)	1
LARYNGEAL OEDEMA	1/171 (0.6%)	1	0/336 (0%)	0
PLEURAL EFFUSION	0/171 (0%)	0	1/336 (0.3%)	1
PLEURITIC PAIN	1/171 (0.6%)	1	0/336 (0%)	0
PNEUMOMEDIASTINUM	0/171 (0%)	0	1/336 (0.3%)	1
PNEUMOTHORAX	1/171 (0.6%)	1	1/336 (0.3%)	1
PULMONARY ARTERY THROMBOSIS	1/171 (0.6%)	1	0/336 (0%)	0
PULMONARY EMBOLISM	1/171 (0.6%)	1	4/336 (1.2%)	5
Skin and subcutaneous tissue disorders
ANGIOEDEMA	1/171 (0.6%)	1	0/336 (0%)	0
Surgical and medical procedures
ABORTION INDUCED	1/171 (0.6%)	1	0/336 (0%)	0
Vascular disorders
AORTIC STENOSIS	0/171 (0%)	0	1/336 (0.3%)	1
DEEP VEIN THROMBOSIS	3/171 (1.8%)	3	0/336 (0%)	0
ILIAC ARTERY OCCLUSION	0/171 (0%)	0	1/336 (0.3%)	1
POOR VENOUS ACCESS	1/171 (0.6%)	1	0/336 (0%)	0
Other (Not Including Serious) Adverse Events
	Veliparib Placebo With Carboplatin and Paclitaxel		Veliparib With Carboplatin and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/171 (98.8%)		332/336 (98.8%)
Blood and lymphatic system disorders
ANAEMIA	114/171 (66.7%)	487	254/336 (75.6%)	1124
LEUKOPENIA	65/171 (38%)	306	133/336 (39.6%)	681
LYMPHOPENIA	14/171 (8.2%)	32	42/336 (12.5%)	135
NEUTROPENIA	156/171 (91.2%)	1259	292/336 (86.9%)	2331
THROMBOCYTOPENIA	118/171 (69%)	568	257/336 (76.5%)	1608
Cardiac disorders
PALPITATIONS	4/171 (2.3%)	4	19/336 (5.7%)	27
TACHYCARDIA	11/171 (6.4%)	13	13/336 (3.9%)	19
Ear and labyrinth disorders
TINNITUS	8/171 (4.7%)	9	20/336 (6%)	42
VERTIGO	11/171 (6.4%)	17	24/336 (7.1%)	37
Eye disorders
DRY EYE	9/171 (5.3%)	10	22/336 (6.5%)	23
Gastrointestinal disorders
ABDOMINAL DISTENSION	7/171 (4.1%)	10	17/336 (5.1%)	17
ABDOMINAL PAIN	20/171 (11.7%)	25	47/336 (14%)	70
ABDOMINAL PAIN UPPER	17/171 (9.9%)	24	53/336 (15.8%)	82
CONSTIPATION	55/171 (32.2%)	75	113/336 (33.6%)	172
DIARRHOEA	61/171 (35.7%)	115	150/336 (44.6%)	310
DRY MOUTH	14/171 (8.2%)	14	32/336 (9.5%)	39
DYSPEPSIA	16/171 (9.4%)	17	60/336 (17.9%)	76
GASTRITIS	9/171 (5.3%)	9	4/336 (1.2%)	5
GASTROOESOPHAGEAL REFLUX DISEASE	7/171 (4.1%)	7	18/336 (5.4%)	19
NAUSEA	107/171 (62.6%)	253	238/336 (70.8%)	702
STOMATITIS	19/171 (11.1%)	26	44/336 (13.1%)	69
TOOTHACHE	10/171 (5.8%)	11	20/336 (6%)	22
VOMITING	60/171 (35.1%)	109	114/336 (33.9%)	261
General disorders
ASTHENIA	42/171 (24.6%)	125	84/336 (25%)	289
CHEST PAIN	9/171 (5.3%)	9	17/336 (5.1%)	27
FATIGUE	85/171 (49.7%)	181	167/336 (49.7%)	369
INFLUENZA LIKE ILLNESS	15/171 (8.8%)	24	24/336 (7.1%)	42
MUCOSAL INFLAMMATION	7/171 (4.1%)	7	30/336 (8.9%)	37
OEDEMA PERIPHERAL	18/171 (10.5%)	22	64/336 (19%)	86
PAIN	9/171 (5.3%)	9	20/336 (6%)	22
PYREXIA	33/171 (19.3%)	42	54/336 (16.1%)	66
Immune system disorders
DRUG HYPERSENSITIVITY	32/171 (18.7%)	65	57/336 (17%)	89
Infections and infestations
INFLUENZA	5/171 (2.9%)	5	17/336 (5.1%)	21
NASOPHARYNGITIS	24/171 (14%)	33	54/336 (16.1%)	79
RESPIRATORY TRACT INFECTION VIRAL	9/171 (5.3%)	14	15/336 (4.5%)	25
RHINITIS	3/171 (1.8%)	3	17/336 (5.1%)	20
SINUSITIS	9/171 (5.3%)	11	24/336 (7.1%)	28
UPPER RESPIRATORY TRACT INFECTION	17/171 (9.9%)	24	46/336 (13.7%)	68
URINARY TRACT INFECTION	14/171 (8.2%)	23	41/336 (12.2%)	75
Investigations
ALANINE AMINOTRANSFERASE INCREASED	24/171 (14%)	58	54/336 (16.1%)	126
ASPARTATE AMINOTRANSFERASE INCREASED	20/171 (11.7%)	56	46/336 (13.7%)	92
BLOOD ALKALINE PHOSPHATASE INCREASED	7/171 (4.1%)	16	23/336 (6.8%)	35
WEIGHT INCREASED	4/171 (2.3%)	12	19/336 (5.7%)	40
Metabolism and nutrition disorders
DECREASED APPETITE	46/171 (26.9%)	56	79/336 (23.5%)	103
DEHYDRATION	3/171 (1.8%)	3	17/336 (5.1%)	23
HYPERGLYCAEMIA	8/171 (4.7%)	18	20/336 (6%)	63
HYPOCALCAEMIA	14/171 (8.2%)	21	29/336 (8.6%)	52
HYPOKALAEMIA	18/171 (10.5%)	40	39/336 (11.6%)	89
HYPOMAGNESAEMIA	36/171 (21.1%)	96	82/336 (24.4%)	178
HYPONATRAEMIA	3/171 (1.8%)	3	18/336 (5.4%)	24
HYPOPHOSPHATAEMIA	8/171 (4.7%)	23	26/336 (7.7%)	50
Musculoskeletal and connective tissue disorders
ARTHRALGIA	39/171 (22.8%)	58	62/336 (18.5%)	85
BACK PAIN	40/171 (23.4%)	51	61/336 (18.2%)	97
BONE PAIN	21/171 (12.3%)	33	39/336 (11.6%)	53
MUSCLE SPASMS	9/171 (5.3%)	11	16/336 (4.8%)	17
MUSCULOSKELETAL CHEST PAIN	8/171 (4.7%)	8	23/336 (6.8%)	26
MUSCULOSKELETAL PAIN	18/171 (10.5%)	26	22/336 (6.5%)	36
MYALGIA	23/171 (13.5%)	33	58/336 (17.3%)	82
PAIN IN EXTREMITY	28/171 (16.4%)	36	66/336 (19.6%)	108
Nervous system disorders
DIZZINESS	29/171 (17%)	46	64/336 (19%)	99
DYSGEUSIA	28/171 (16.4%)	38	66/336 (19.6%)	99
HEADACHE	58/171 (33.9%)	91	120/336 (35.7%)	198
NEUROPATHY PERIPHERAL	13/171 (7.6%)	16	20/336 (6%)	25
PARAESTHESIA	16/171 (9.4%)	27	29/336 (8.6%)	36
PERIPHERAL SENSORY NEUROPATHY	88/171 (51.5%)	180	156/336 (46.4%)	344
Psychiatric disorders
ANXIETY	11/171 (6.4%)	14	38/336 (11.3%)	43
DEPRESSION	9/171 (5.3%)	10	29/336 (8.6%)	33
INSOMNIA	26/171 (15.2%)	30	61/336 (18.2%)	80
Reproductive system and breast disorders
BREAST PAIN	10/171 (5.8%)	12	16/336 (4.8%)	21
Respiratory, thoracic and mediastinal disorders
COUGH	28/171 (16.4%)	35	70/336 (20.8%)	101
DYSPNOEA	32/171 (18.7%)	37	68/336 (20.2%)	101
DYSPNOEA EXERTIONAL	7/171 (4.1%)	17	20/336 (6%)	24
EPISTAXIS	29/171 (17%)	37	62/336 (18.5%)	87
OROPHARYNGEAL PAIN	14/171 (8.2%)	15	27/336 (8%)	36
PRODUCTIVE COUGH	8/171 (4.7%)	13	18/336 (5.4%)	22
RHINORRHOEA	4/171 (2.3%)	5	19/336 (5.7%)	28
Skin and subcutaneous tissue disorders
ALOPECIA	87/171 (50.9%)	110	181/336 (53.9%)	250
DRY SKIN	6/171 (3.5%)	7	25/336 (7.4%)	27
ERYTHEMA	9/171 (5.3%)	18	18/336 (5.4%)	20
PRURITUS	4/171 (2.3%)	6	29/336 (8.6%)	39
RASH	20/171 (11.7%)	25	38/336 (11.3%)	51
Vascular disorders
HOT FLUSH	12/171 (7%)	15	36/336 (10.7%)	45
HYPERTENSION	7/171 (4.1%)	8	21/336 (6.3%)	33
LYMPHOEDEMA	11/171 (6.4%)	14	19/336 (5.7%)	19

Limitations/Caveats

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Principal Investigators are NOT employed by the organization sponsoring the study.

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