TRITON2: A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02952534
• Collaborator: Foundation Medicine (Industry)
• Enrollment: 277
• Locations: 149
• Arm: 1
• Actual Duration (Months): 53.3
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration Resistant Prostate Cancer	Drug: Rucaparib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 277 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer Associated With Homologous Recombination Deficiency
• Actual Study Start Date: Feb 15, 2017
• Actual Primary Completion Date: Jul 18, 2021
• Actual Study Completion Date: Jul 27, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rucaparib Oral rucaparib (monotherapy)	Drug: Rucaparib; Rucaparib will be administered daily; Other Names: CO-338

Outcome Measures

Primary Outcome Measures

1. Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR) [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   The primary efficacy endpoint is confirmed radiographic ORR by central IRR. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

1. Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV) [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A supportive efficacy endpoint is confirmed radiographic ORR by INV. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

2. Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR) [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A secondary efficacy endpoint is DOR by central IRR. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.

3. Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A secondary efficacy endpoint is DOR as assessed by the investigator. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.

4. Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory [PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.]

   A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 50% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 50% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.

5. Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory [PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.]

   A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 90% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 90% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.

6. Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR) [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by IRR. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by IRR using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.

7. Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by Investigator. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.

8. Overall Survival (OS) by Gene [From date of first dose until event, loss to follow-up, withdrawal of consent, or study closure: an overall median of approximately 33.1 months]

   A secondary efficacy endpoint is Overall Survival (OS). OS is defined as the date from first dose of rucaparib to the date of death due to any cause, +1 day.

9. Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR) [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

   A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by IRR. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.

10. Clinical Benefit Rate (CBR) by Gene Per Investigator [Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.]

    A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by Investigator. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.

11. Time to PSA Progression by Gene [PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.]

    A secondary efficacy endpoint is time to PSA progession. Time to PSA progression is defined as the time from first dose of rucaparib to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline if there was no PSA decline after baseline) in PSA was measured, plus 1 day. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later (unless the PSA progression occurred at the last recorded PSA assessment). If confirmed, the date used for time of PSA progression is the earlier of the 2 PSA dates.

12. Steady State Trough (Cmin) Level Rucaparib Concentrations [Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113]

    Trough (Cmin) concentrations of rucaparib are summarized for all patients with at least one PK sample collected. The absolute values of rucaparib plasma concentration at each time point are presented by gene.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be 18 years old at the time the informed consent form is signed

• Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate

• Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)

• Experienced disease progression after having received at least 1 but no more than 2 prior next-generation androgen receptor-targeted therapies, and 1 prior taxane-based chemotherapy, for castration-resistant disease

• Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency

Exclusion Criteria:

• Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer

• Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy

• Symptomatic and/or untreated central nervous system metastases

• Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Mayo Clinc	Phoenix	Arizona	United States	85259
3	Arizona Oncology Associates	Tucson	Arizona	United States	85704
4	Alliance Research Centers	Laguna Hills	California	United States	92653
5	VA Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
6	University of Southern California	Los Angeles	California	United States	90211
7	Stanford University	Palo Alto	California	United States	94305
8	Sharp Memorial Hospital	San Diego	California	United States	92123
9	Pacific Hematology Oncology Associates	San Francisco	California	United States	94115
10	San Francisco VA Health Care System	San Francisco	California	United States	94143
11	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94158
12	Redwood Regional Medical Group	Santa Rosa	California	United States	95406
13	Kaiser Permanente Medical Center (Vallejo)	Vallejo	California	United States	94589
14	Rocky Mountain Cancer Centers	Aurora	Colorado	United States	80012
15	Yale School of Medicine	New Haven	Connecticut	United States	06510
16	4701 Ogletown Stanton Rd.	Newark	Delaware	United States	19713
17	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
18	Boca Raton Community Hospital, Inc.	Boca Raton	Florida	United States	33486
19	Florida Cancer Specialists	Fort Myers	Florida	United States	33980
20	University of Florida Health Cancer Center	Orlando	Florida	United States	32806
21	Moffitt Cancer Center	Tampa	Florida	United States	33612
22	Atlanta Urological Group	Atlanta	Georgia	United States	30312
23	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
24	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
25	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
26	Walter Reed Hospital	Bethesda	Maryland	United States	48202
27	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
28	VA Ann Arbor Healthcare System	Ann Arbor	Michigan	United States	48105
29	Henry Ford Hospital	Detroit	Michigan	United States	48202
30	Fairview Hospital	Edina	Minnesota	United States	55435
31	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
32	Minnesota Veterans Research Institute	Minneapolis	Minnesota	United States	55417
33	HCA Midwest Division - Kansas City	Kansas City	Missouri	United States	64132
34	Alegent Health Bergan Mercy Hospital , GU Research Network	Omaha	Nebraska	United States	68130
35	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
36	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89119
37	Premier Urology Associates dba/AdvanceMed Research	Lawrenceville	New Jersey	United States	08648
38	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
39	Roswell Park	Buffalo	New York	United States	14263
40	NYU Perlmutter Cancer Center	New York	New York	United States	10016
41	Memorial Sloan Kettering CC	New York	New York	United States	10065
42	Weill Cornell Medical College/NewYork-Presbyterian Hospital	New York	New York	United States	10065
43	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York	United States	12301
44	University of Rochester	Rochester	New York	United States	14642
45	SUNY Upstate Medical University	Syracuse	New York	United States	13210
46	Carolina Urology Partners	Concord	North Carolina	United States	28025
47	The Urology Group	Cincinnati	Ohio	United States	45212
48	Kettering Cancer Center	Kettering	Ohio	United States	45429
49	Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
50	VA Portland Health Care System	Portland	Oregon	United States	97219
51	Consultants in Medical Oncology Hematology	Horsham	Pennsylvania	United States	19044
52	SCRI - Tennessee Oncology	Nashville	Tennessee	United States	37203
53	Texas Oncology Medical City Dallas	Dallas	Texas	United States	75320
54	UT Southwestern Medical Center	Dallas	Texas	United States	75390
55	UT Health Science Center	Houston	Texas	United States	77030
56	Texas Oncology - Tyler	Tyler	Texas	United States	75702
57	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
58	VA Puget Sound	Seattle	Washington	United States	98108
59	Northern Cancer Insitute, St. Leonards	Saint Leonards	New South Wales	Australia	2065
60	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
61	Peninsula & Southeast Oncology	Frankston	Victoria	Australia	3199
62	Barwon Health, University Hospital Geelong	Geelong	Victoria	Australia	3220
63	Cabrini Hospital	Malvern	Victoria	Australia	3144
64	Southside Cancer Care Centre	Miranda		Australia	2228
65	Orange Health Services	Orange		Australia	2800
66	St John of God Hospital, Subiaco	Subiaco		Australia	6008
67	Riverina Cancer Care Centre	Wagga Wagga		Australia	2650
68	ZNA Middelheim	Antwerp		Belgium	2020
69	Universitair Ziekenhuis Gent	Gent		Belgium	B-9000
70	AZ Groeninge	Kortrijk		Belgium	8500
71	CHU Sart-Tilman	Liège		Belgium	4000
72	Equipe de Recherche Clinique, Département d'Oncologie/Hématologie	Liège		Belgium	4000
73	AZ DELTA	Roeselare		Belgium	B-8800
74	Juravinski Cancer Centre Hamilton Health Services	Hamilton	Ontario	Canada	L8V5C2
75	London Health Science Center - Victoria Hospital	London	Ontario	Canada	N6A 4L6
76	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H8L6
77	Princess Margaret Hospital	Toronto		Canada	M5G 2M9
78	Copenhagen University Hospital	Copenhagen		Denmark	2100
79	Herlev Hospital	Herlev		Denmark	2730
80	Vejle Sygehus	Vejle		Denmark	7100
81	Centre François Baclesse	Caen		France	14000
82	Centre Georges François Leclerc	Dijon		France	21079
83	Clinique Victor Hugo Centre Jean Bernard	Le Mans		France	72000
84	Hôpital Privé La Louvière	Lille		France	59800
85	Polyclinique de Gentilly (Centre D'Oncologie De Gentilly)	Nancy		France	54100
86	Institut Curie	Paris		France	75248
87	Hôpital Privé des Côtes d'Armor	Plérin		France	22190
88	CRLCC Eugene Marquis	Rennes		France	35042
89	Gemeinschaftspraxis fur Hamatologie & Onkologie	Augsburg		Germany	86150
90	Charite Universitatsmedizin Berlin	Berlin		Germany	12200
91	Universitatsklinikum Carl Gustav Carus	Dresden		Germany	01307
92	Universitatsklinikum Dusseldorf	Dusseldorf		Germany	40225
93	Urologische Gemeinschaftspraxis	Emmendingen		Germany	79312
94	Universitaetsklinikum Hamburg-Eppendorf (UKE)	Hamburg		Germany	20246
95	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
96	Universitatsklinikum Jena	Jena		Germany	07747
97	Universitätsklinik Köln	Köln		Germany	50937
98	Universitätsklinikum Schleswig-Holstein	Lübeck		Germany	23538
99	Medizinischen Fakultät Mannheim der Universität Heidelberg	Mannheim		Germany	68167
100	Studienpraxis Urologie	Nürtingen		Germany	72622
101	University of Tuebingen	Tuebingen		Germany	72076
102	Die Gesundhehitsunion DGU	Wuppertal		Germany	42103
103	Cork University Hospital	Cork		Ireland	T12 DFK4
104	St. Vincent's University Hospital	Dublin		Ireland	D04T6F4
105	St James's Hospital	Dublin		Ireland	D08 NHY1
106	Adelaide & Meath Hospital, Incorporating the National Children's Hospital	Dublin		Ireland	Dublin 24
107	Mater Misericordiae University Hospital	Dublin		Ireland	Dublin 7
108	Rambam Health Care Campus (RHCC), Rambam Medical Center	Haifa		Israel	3109601
109	Hadassah University Hospital	Jerusalem		Israel	71120
110	Meir Medical Center	Kfar Saba		Israel	4428164
111	Rabin Medical Center-Beilinson Campus	Petach Tikva		Israel	4941492
112	Chaim Sheba Medical Center	Ramat Gan		Israel	52621
113	The Tel Aviv Sourasky Medical Center (Ichilov Hospital)	Tel Aviv		Israel	64231
114	Ospedale San Donato, Azienda USLSUDEST	Arezzo		Italy	52100
115	Ospedale Santa Maria delle Croci	Faenza		Italy	48018
116	IRCCS Istituto Nazionale dei Tumori (INT)	Milano		Italy	20133
117	IEO Instituto Europeo di Oncologia	Milano		Italy	20141
118	University of Modena and Reggio Emilia Medical Oncology	Modena		Italy	41124
119	Azienda Ospedaliera San Camillo-Forlanini	Rome		Italy	00152
120	Azienda Opsedaliera S. Maria di Terni	Terni		Italy	05100
121	Santa Chiara Hospital, Dept Medical Oncology	Trento		Italy	38122
122	Hospital Universitari Germans Trias i Pujol	Badalona		Spain	08916
123	Hospital del Mar, Servicio de Oncología	Barcelona		Spain	08003
124	Hospital Clínic i Provincial de Barcelona-Oncology	Barcelona		Spain	08036
125	Instituto Catalan de Oncologia	Barcelona		Spain	08908
126	Hospital Universitari Germans Trias i Pujol	Barcelona		Spain	08916
127	Hospital General Universitario de Guadalajara	Guadalajara		Spain	19002
128	Hospital Universitario Lucus Augusti.	Lugo		Spain	27003
129	MD Anderson Cancer Center - Madrid	Madrid		Spain	28033
130	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
131	Hospital 12 de Octubre	Madrid		Spain	28041
132	Hospital Universitario La Paz	Madrid		Spain	28046
133	Hospital Puerta de Hierro-Majadahonda	Madrid		Spain	28222
134	Hospital Universitario Central de Asturias	Oviedo		Spain	33011
135	Corporacio Sanitaria Parc Tauli	Sabadell		Spain	8208
136	Marques de Valdecilla University Hospital (HUMV)	Santander		Spain	39008
137	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
138	Instituto Valenciano de Oncologia IVO	Valencia		Spain	46009
139	Wexham Park Hospital	Slough	Berkshire	United Kingdom	SL2 4HL
140	Mount Vernon Cancer Centre	Northwood	England	United Kingdom	HA6 2RN
141	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
142	Oxford University Hospitals	Headington		United Kingdom	OC3 7LJ
143	Royal Liverpool Hospital	Liverpool		United Kingdom	L7 8XP
144	London Health Science Center - Victoria Hospital	London		United Kingdom	N6A 4L6
145	Guy's Hospital	London		United Kingdom	SE1 9RT
146	Sarah Cannon Research Institutute - UK	London		United Kingdom	W1G 6AD
147	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
148	Musgrove Park Hospital	Taunton		United Kingdom	TA1 5DA
149	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral		United Kingdom	CH63 4JY

Sponsors and Collaborators

• Clovis Oncology, Inc.
• Foundation Medicine

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2020
• Statistical Analysis Plan - Jul 2, 2019

More Information

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02952534
• Other Study ID Numbers: CO-338-052
• First Posted: Nov 2, 2016
• Last Update Posted: Jul 6, 2022
• Last Verified: Jun 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
• Keywords provided by Clovis Oncology, Inc.: CRPC; PARP inhibitor; PARPi; BRCA; ATM; HRD; TRITON; homologous recombination; DNA repair; DNA defect; DNA anomaly; BARD1; BRIP1; CDK12; CHEK2; FANCA; NBN; PALB2; RAD51; RAD51B; RAD51C; RAD51D; RAD54L; germline; somatic; mCRPC
• Additional relevant MeSH terms: Prostatic Neoplasms; Rucaparib

Study Results

Participant Flow

Recruitment Details	A total of 277 patients were recruited from 102 sites across 12 countries.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Period Title: Overall Study
STARTED	172	59	14	7	25
COMPLETED	172	59	14	7	25
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation	Total
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.	Total of all reporting groups
Overall Participants	172	59	14	7	25	277
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	72	73	64	65	70	71
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	172 100%	59 100%	14 100%	7 100%	25 100%	277 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 1.7%	0 0%	0 0%	1 14.3%	1 4%	5 1.8%
Native Hawaiian or Other Pacific Islander	1 0.6%	0 0%	0 0%	0 0%	0 0%	1 0.4%
Black or African American	8 4.7%	3 5.1%	1 7.1%	0 0%	4 16%	16 5.8%
White	127 73.8%	43 72.9%	6 42.9%	5 71.4%	17 68%	198 71.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	33 19.2%	13 22%	7 50%	1 14.3%	3 12%	57 20.6%

Outcome Measures

1. Primary Outcome

Title	Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR)
Description	The primary efficacy endpoint is confirmed radiographic ORR by central IRR. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

IRR Efficacy Population - The IRR efficacy population is defined by measurable disease status at baseline using modified RECIST Version 1.1 criteria per independent radiology review.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	81	23	8	4	17
Number (95% Confidence Interval) [percentage of participants]	45.7 26.6%	0.0 0%	0.0 0%	0.0 0%	41.2 164.8%

2. Secondary Outcome

Title	Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)
Description	A supportive efficacy endpoint is confirmed radiographic ORR by INV. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Investigator Efficacy Population - The Investigator efficacy population is defined by measurable disease status at baseline using modified RECIST Version 1.1 criteria per the investigator (INV).

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	87	21	9	4	17
Number (95% Confidence Interval) [percentage of participants]	48.3 28.1%	9.5 16.1%	0.0 0%	25.0 357.1%	41.2 164.8%

3. Secondary Outcome

Title	Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR)
Description	A secondary efficacy endpoint is DOR by central IRR. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Patients with a confirmed response in the IRR Efficacy Population. The IRR efficacy population is defined by measurable disease status at baseline using modified RECIST Version 1.1 criteria per independent radiology review. Note, there were no patients with confirmed response by IRR in the ATM, CDK12 and CHEK2 arms.

Arm/Group Title	BRCA Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	37	7
Median (95% Confidence Interval) [months]	15.5	22.1

4. Secondary Outcome

Title	Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator
Description	A secondary efficacy endpoint is DOR as assessed by the investigator. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Patients with a confirmed response in the Investigator Efficacy Population. The Investigator efficacy population is defined by measurable disease status at baseline using modified RECIST Version 1.1 criteria per the investigator. Note, there were no patients with confirmed response by investigator in the CDK12 arm.

Arm/Group Title	BRCA Mutation	ATM Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	42	2	1	7
Median (95% Confidence Interval) [months]	6.6	7.5	16.6	18.4

5. Secondary Outcome

Title	Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory
Description	A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 50% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 50% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.
Time Frame	PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.

Outcome Measure Data

Analysis Population Description

All patients who had a PSA value at baseline.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Number (95% Confidence Interval) [percentage of participants]	53.5 31.1%	3.4 5.8%	7.1 50.7%	14.3 204.3%	36.0 144%

6. Secondary Outcome

Title	Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory
Description	A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 90% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 90% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.
Time Frame	PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.

Outcome Measure Data

Analysis Population Description

All patients who had a PSA value at baseline.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Number (95% Confidence Interval) [percentage of participants]	19.8 11.5%	0 0%	0 0%	14.3 204.3%	16.0 64%

7. Secondary Outcome

Title	Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)
Description	A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by IRR. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by IRR using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

All patients

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Median (95% Confidence Interval) [months]	10.7	5.3	3.7	9.4	11.6

8. Secondary Outcome

Title	Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator
Description	A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by Investigator. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

All patients

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Median (95% Confidence Interval) [months]	9.6	7.8	3.7	3.5	11.6

9. Secondary Outcome

Title	Overall Survival (OS) by Gene
Description	A secondary efficacy endpoint is Overall Survival (OS). OS is defined as the date from first dose of rucaparib to the date of death due to any cause, +1 day.
Time Frame	From date of first dose until event, loss to follow-up, withdrawal of consent, or study closure: an overall median of approximately 33.1 months

Outcome Measure Data

Analysis Population Description

Safety Population - The safety population consists of all patients who received at least 1 dose of protocol-specified treatment.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Median (95% Confidence Interval) [months]	17.2	14.6	13.9	11.1	11.6

10. Secondary Outcome

Title	Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)
Description	A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by IRR. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

All patients

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
6 months	100 58.1%	10 16.9%	2 14.3%	2 28.6%	13 52%
12 months	36 20.9%	3 5.1%	0 0%	1 14.3%	6 24%

11. Secondary Outcome

Title	Clinical Benefit Rate (CBR) by Gene Per Investigator
Description	A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by Investigator. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.
Time Frame	Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

All patients

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
6 months	103 59.9%	17 28.8%	3 21.4%	2 28.6%	14 56%
12 months	39 22.7%	6 10.2%	1 7.1%	1 14.3%	6 24%

12. Secondary Outcome

Title	Time to PSA Progression by Gene
Description	A secondary efficacy endpoint is time to PSA progession. Time to PSA progression is defined as the time from first dose of rucaparib to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline if there was no PSA decline after baseline) in PSA was measured, plus 1 day. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later (unless the PSA progression occurred at the last recorded PSA assessment). If confirmed, the date used for time of PSA progression is the earlier of the 2 PSA dates.
Time Frame	PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.

Outcome Measure Data

Analysis Population Description

All patients who had a PSA value at baseline.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	172	59	14	7	25
Median (95% Confidence Interval) [months]	6.5	3.1	3.5	5.6	5.3

13. Secondary Outcome

Title	Steady State Trough (Cmin) Level Rucaparib Concentrations
Description	Trough (Cmin) concentrations of rucaparib are summarized for all patients with at least one PK sample collected. The absolute values of rucaparib plasma concentration at each time point are presented by gene.
Time Frame	Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113

Outcome Measure Data

Analysis Population Description

Safety population with at least one PK sample collected. The safety population consists of all patients who received at least 1 dose of protocol-specified treatment.

Arm/Group Title	BRCA Mutation	ATM Mutation	CDK12 Mutation	CHEK2 Mutation	Other Gene Mutation
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.	Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.	Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.	Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.	Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
Measure Participants	101	51	14	5	13
Day 29	1539.565 (966.2604)	1605.002 (856.2478)	1639.357 (1428.5691)	1286.998 (1138.2119)	1189.845 (748.3045)
Day 57	1578.353 (1057.8049)	1600.380 (1198.3899)	1405.167 (806.4642)	1841.667 (2106.3362)	1792.499 (1672.7732)
Day 85	1308.704 (693.6717)	1505.400 (802.0812)	1699.700 (991.9922)	815.500 (557.9073)	2255.889 (1831.9626)
Day 113	1533.690 (889.6130)	1515.300 (1291.8497)	1520.700 (884.1374)	728.000 (469.5189)	1433.875 (637.4535)

Adverse Events

Time Frame	Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 4.5 years.
Arm/Group Title	All Patients
Arm/Group Description	All patients received open-label oral rucaparib 600 mg BID (twice a day) in continuous 28-day cycles.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	8/277 (2.9%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	96/277 (34.7%)
Blood and lymphatic system disorders
Anaemia	14/277 (5.1%)
Anaemia of malignant disease	1/277 (0.4%)
Aplastic anaemia	1/277 (0.4%)
Leukopenia	1/277 (0.4%)
Neutropenia	1/277 (0.4%)
Pancytopenia	2/277 (0.7%)
Cardiac disorders
Acute coronary syndrome	3/277 (1.1%)
Acute myocardial infarction	3/277 (1.1%)
Atrial fibrillation	1/277 (0.4%)
Cardiac failure	1/277 (0.4%)
Coronary artery occlusion	1/277 (0.4%)
Torsade de pointes	1/277 (0.4%)
Ventricular tachycardia	1/277 (0.4%)
Gastrointestinal disorders
Abdominal pain	1/277 (0.4%)
Colitis	1/277 (0.4%)
Diarrhoea	3/277 (1.1%)
Gastrointestinal haemorrhage	1/277 (0.4%)
Gastrooesophageal reflux disease	1/277 (0.4%)
Ileus	1/277 (0.4%)
Intestinal ischaemia	1/277 (0.4%)
Mechanical ileus	1/277 (0.4%)
Nausea	2/277 (0.7%)
Oesophagitis	1/277 (0.4%)
Rectal haemorrhage	1/277 (0.4%)
Small intestinal obstruction	1/277 (0.4%)
Vomiting	3/277 (1.1%)
General disorders
Asthenia	2/277 (0.7%)
Fatigue	2/277 (0.7%)
Non-cardiac chest pain	1/277 (0.4%)
Pain	2/277 (0.7%)
Pyrexia	1/277 (0.4%)
Infections and infestations
Abscess oral	1/277 (0.4%)
Bacteraemia	1/277 (0.4%)
Cellulitis	1/277 (0.4%)
Device related infection	2/277 (0.7%)
Fournier's gangrene	1/277 (0.4%)
Gastroenteritis	1/277 (0.4%)
Haemophilus infection	1/277 (0.4%)
Infective exacerbation of chronic obstructive airways disease	2/277 (0.7%)
Legionella infection	1/277 (0.4%)
Paraspinal abscess	1/277 (0.4%)
Pneumonia	6/277 (2.2%)
Pneumonia legionella	1/277 (0.4%)
Pneumonia staphylococcal	1/277 (0.4%)
Pulmonary sepsis	1/277 (0.4%)
Sepsis	4/277 (1.4%)
Upper respiratory tract infection	1/277 (0.4%)
Urinary tract infection	4/277 (1.4%)
Urosepsis	4/277 (1.4%)
Wound infection	1/277 (0.4%)
Injury, poisoning and procedural complications
Fall	2/277 (0.7%)
Foot fracture	1/277 (0.4%)
Postoperative respiratory failure	1/277 (0.4%)
Spinal compression fracture	1/277 (0.4%)
Urinary tract stoma complication	1/277 (0.4%)
Investigations
Blood creatinine increased	2/277 (0.7%)
Metabolism and nutrition disorders
Dehydration	2/277 (0.7%)
Electrolyte imbalance	1/277 (0.4%)
Failure to thrive	1/277 (0.4%)
Hypocalcaemia	1/277 (0.4%)
Hypoglycaemia	2/277 (0.7%)
Hypokalaemia	1/277 (0.4%)
Hyponatraemia	2/277 (0.7%)
Musculoskeletal and connective tissue disorders
Back pain	2/277 (0.7%)
Muscular weakness	2/277 (0.7%)
Musculoskeletal pain	1/277 (0.4%)
Pain in extremity	2/277 (0.7%)
Pathological fracture	5/277 (1.8%)
Spinal pain	1/277 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/277 (0.4%)
Bladder cancer	1/277 (0.4%)
Chronic lymphocytic leukaemia	1/277 (0.4%)
Malignant neoplasm progression	1/277 (0.4%)
Nervous system disorders
Cerebellar infarction	1/277 (0.4%)
Cerebral haemorrhage	1/277 (0.4%)
Cerebrovascular accident	1/277 (0.4%)
Dizziness	1/277 (0.4%)
Dysarthria	1/277 (0.4%)
Ischaemic stroke	1/277 (0.4%)
Presyncope	1/277 (0.4%)
Sacral radiculopathy	1/277 (0.4%)
Sciatica	1/277 (0.4%)
Seizure	2/277 (0.7%)
Spinal cord compression	1/277 (0.4%)
Syncope	2/277 (0.7%)
Psychiatric disorders
Confusional state	2/277 (0.7%)
Renal and urinary disorders
Acute kidney injury	7/277 (2.5%)
Haematuria	6/277 (2.2%)
Hydronephrosis	1/277 (0.4%)
Urinary retention	3/277 (1.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/277 (0.4%)
Chronic obstructive pulmonary disease	1/277 (0.4%)
Dyspnoea	2/277 (0.7%)
Epistaxis	1/277 (0.4%)
Pulmonary embolism	2/277 (0.7%)
Vascular disorders
Embolism	1/277 (0.4%)
Hypertension	1/277 (0.4%)
Peripheral ischaemia	1/277 (0.4%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	274/277 (98.9%)
Blood and lymphatic system disorders
Anaemia	129/277 (46.6%)
Neutropenia	20/277 (7.2%)
Thrombocytopenia	33/277 (11.9%)
Gastrointestinal disorders
Abdominal pain	16/277 (5.8%)
Constipation	76/277 (27.4%)
Diarrhoea	65/277 (23.5%)
Dyspepsia	18/277 (6.5%)
Nausea	139/277 (50.2%)
Vomiting	67/277 (24.2%)
General disorders
Asthenia	50/277 (18.1%)
Fatigue	131/277 (47.3%)
Oedema peripheral	50/277 (18.1%)
Pyrexia	15/277 (5.4%)
Infections and infestations
Upper respiratory tract infection	19/277 (6.9%)
Urinary tract infection	37/277 (13.4%)
Injury, poisoning and procedural complications
Fall	18/277 (6.5%)
Investigations
Alanine aminotransferase increased	72/277 (26%)
Aspartate aminotransferase increased	71/277 (25.6%)
Blood alkaline phosphatase increased	18/277 (6.5%)
Blood creatinine increased	50/277 (18.1%)
Platelet count decreased	32/277 (11.6%)
Weight decreased	45/277 (16.2%)
Metabolism and nutrition disorders
Decreased appetite	96/277 (34.7%)
Dehydration	14/277 (5.1%)
Hypocalcaemia	21/277 (7.6%)
Hypophosphataemia	27/277 (9.7%)
Musculoskeletal and connective tissue disorders
Althralgia	44/277 (15.9%)
Back pain	50/277 (18.1%)
Bone pain	18/277 (6.5%)
Muscular weakness	17/277 (6.1%)
Musculoskeletal chest pain	14/277 (5.1%)
Musculoskeletal pain	33/277 (11.9%)
Myalgia	14/277 (5.1%)
Pain in extremity	32/277 (11.6%)
Nervous system disorders
Dizziness	53/277 (19.1%)
Dysgeusia	32/277 (11.6%)
Headache	28/277 (10.1%)
Neuropathy peripheral	14/277 (5.1%)
Psychiatric disorders
Insomnia	18/277 (6.5%)
Renal and urinary disorders
Haematuria	21/277 (7.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	40/277 (14.4%)
Cough	33/277 (11.9%)
Skin and subcutaneous tissue disorders
Dry skin	18/277 (6.5%)
Photosensitivity reaction	19/277 (6.9%)
Rash	22/277 (7.9%)
Vascular disorders
Hypertension	20/277 (7.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.