Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02975934




Registration number
NCT02975934
Ethics application status
Date submitted
19/11/2016
Date registered
29/11/2016
Date last updated
20/03/2024

Titles & IDs
Public title
A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
Scientific title
TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency
Secondary ID [1] 0 0
CO-338-063
Universal Trial Number (UTN)
Trial acronym
TRITON3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration Resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rucaparib
Treatment: Drugs - Abiraterone acetate or Enzalutamide or Docetaxel

Experimental: Rucaparib - Oral rucaparib (monotherapy).

Active comparator: Abiraterone acetate or Enzalutamide or Docetaxel - Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).


Treatment: Drugs: Rucaparib
Rucaparib will be administered daily.

Treatment: Drugs: Abiraterone acetate or Enzalutamide or Docetaxel
Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration
Timepoint [1] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Primary outcome [2] 0 0
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
Timepoint [2] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcome [1] 0 0
Interim Overall Survival in Participants With a BRCA Alteration
Timepoint [1] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [2] 0 0
Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined
Timepoint [2] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [3] 0 0
Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration
Timepoint [3] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcome [4] 0 0
Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined
Timepoint [4] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcome [5] 0 0
Duration of Response (DOR) by IRR in Participants With a BRCA Alteration
Timepoint [5] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcome [6] 0 0
Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined
Timepoint [6] 0 0
From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
Secondary outcome [7] 0 0
PSA Response in Participants With a BRCA Alteration
Timepoint [7] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [8] 0 0
PSA Response in Participants With a BRCA or ATM Alteration Combined
Timepoint [8] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [9] 0 0
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration
Timepoint [9] 0 0
From enrollment to 6 months
Secondary outcome [10] 0 0
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined
Timepoint [10] 0 0
From enrollment to 6 months
Secondary outcome [11] 0 0
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration
Timepoint [11] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [12] 0 0
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined
Timepoint [12] 0 0
From enrollment to primary completion of study (up to approximately 5 years)
Secondary outcome [13] 0 0
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P
Timepoint [13] 0 0
From enrollment to up to approximately 25 weeks
Secondary outcome [14] 0 0
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF
Timepoint [14] 0 0
From enrollment to up to approximately 25 weeks
Secondary outcome [15] 0 0
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L
Timepoint [15] 0 0
From enrollment to up to approximately 25 weeks
Secondary outcome [16] 0 0
Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling
Timepoint [16] 0 0
From enrollment to week 5 of dosing

Eligibility
Key inclusion criteria
* Be 18 years old at the time the informed consent is signed
* Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
* Be surgically or medically castrated, with serum testosterone levels of = 50 ng/dL (1.73 nM)
* Be eligible for treatment with physician's choice of comparator treatment (abiraterone acetate, enzalutamide or docetaxel)
* Experienced disease progression after having received 1 prior next generation androgen receptor-targeted therapy
* Have a deleterious mutation in a BRCA1/2 or ATM gene
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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
* Prior treatment with chemotherapy for metastatic castration-resistant prostate cancer
* 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 study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
405
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [2] 0 0
Orange Health Service - Orange
Recruitment hospital [3] 0 0
Northern Cancer Insitute, St. Leonards - Saint Leonards
Recruitment hospital [4] 0 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [5] 0 0
Peninsula & Southeast Oncology - Frankston
Recruitment hospital [6] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [7] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [8] 0 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment postcode(s) [1] 0 0
2228 - Miranda
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment postcode(s) [7] 0 0
7000 - Hobart
Recruitment postcode(s) [8] 0 0
2650 - Wagga Wagga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Belgium
State/province [26] 0 0
Antwerp
Country [27] 0 0
Belgium
State/province [27] 0 0
Kortrijk
Country [28] 0 0
Belgium
State/province [28] 0 0
Liège
Country [29] 0 0
Belgium
State/province [29] 0 0
Namur
Country [30] 0 0
Canada
State/province [30] 0 0
Alberta
Country [31] 0 0
Canada
State/province [31] 0 0
Manitoba
Country [32] 0 0
Canada
State/province [32] 0 0
New Brunswick
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Oshawa
Country [35] 0 0
Canada
State/province [35] 0 0
Toronto
Country [36] 0 0
Denmark
State/province [36] 0 0
Copenhagen
Country [37] 0 0
Denmark
State/province [37] 0 0
Herlev
Country [38] 0 0
Denmark
State/province [38] 0 0
Vejle
Country [39] 0 0
France
State/province [39] 0 0
Dijon
Country [40] 0 0
France
State/province [40] 0 0
Le Mans
Country [41] 0 0
France
State/province [41] 0 0
Lille
Country [42] 0 0
France
State/province [42] 0 0
Lyon
Country [43] 0 0
France
State/province [43] 0 0
Nancy
Country [44] 0 0
France
State/province [44] 0 0
Paris
Country [45] 0 0
France
State/province [45] 0 0
Plérin
Country [46] 0 0
France
State/province [46] 0 0
Rennes
Country [47] 0 0
France
State/province [47] 0 0
Villejuif
Country [48] 0 0
Germany
State/province [48] 0 0
Augsburg
Country [49] 0 0
Germany
State/province [49] 0 0
Berlin
Country [50] 0 0
Germany
State/province [50] 0 0
Braunschweig
Country [51] 0 0
Germany
State/province [51] 0 0
Dresden
Country [52] 0 0
Germany
State/province [52] 0 0
Dusseldorf
Country [53] 0 0
Germany
State/province [53] 0 0
Emmendingen
Country [54] 0 0
Germany
State/province [54] 0 0
Hamburg
Country [55] 0 0
Germany
State/province [55] 0 0
Jena
Country [56] 0 0
Germany
State/province [56] 0 0
Köln
Country [57] 0 0
Germany
State/province [57] 0 0
Lubeck
Country [58] 0 0
Germany
State/province [58] 0 0
Mannheim
Country [59] 0 0
Germany
State/province [59] 0 0
Nurtingen
Country [60] 0 0
Germany
State/province [60] 0 0
Tuebingen
Country [61] 0 0
Germany
State/province [61] 0 0
Wuppertal
Country [62] 0 0
Ireland
State/province [62] 0 0
Cork
Country [63] 0 0
Ireland
State/province [63] 0 0
Dublin
Country [64] 0 0
Israel
State/province [64] 0 0
Haifa
Country [65] 0 0
Israel
State/province [65] 0 0
Jerusalem
Country [66] 0 0
Israel
State/province [66] 0 0
Kfar Saba
Country [67] 0 0
Israel
State/province [67] 0 0
Petach Tikva
Country [68] 0 0
Israel
State/province [68] 0 0
Tel Aviv
Country [69] 0 0
Israel
State/province [69] 0 0
Tel Hashomer
Country [70] 0 0
Italy
State/province [70] 0 0
Arezzo
Country [71] 0 0
Italy
State/province [71] 0 0
Faenza
Country [72] 0 0
Italy
State/province [72] 0 0
Meldola
Country [73] 0 0
Italy
State/province [73] 0 0
Milano
Country [74] 0 0
Italy
State/province [74] 0 0
Modena
Country [75] 0 0
Italy
State/province [75] 0 0
Roma
Country [76] 0 0
Italy
State/province [76] 0 0
Terni
Country [77] 0 0
Italy
State/province [77] 0 0
Trento
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
Córdoba
Country [80] 0 0
Spain
State/province [80] 0 0
Guadalajara
Country [81] 0 0
Spain
State/province [81] 0 0
Lugo
Country [82] 0 0
Spain
State/province [82] 0 0
Madrid
Country [83] 0 0
Spain
State/province [83] 0 0
Málaga
Country [84] 0 0
Spain
State/province [84] 0 0
Oviedo
Country [85] 0 0
Spain
State/province [85] 0 0
Sabadell
Country [86] 0 0
Spain
State/province [86] 0 0
Santander
Country [87] 0 0
Spain
State/province [87] 0 0
Sevilla
Country [88] 0 0
Spain
State/province [88] 0 0
Valencia
Country [89] 0 0
United Kingdom
State/province [89] 0 0
England
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Cardiff
Country [91] 0 0
United Kingdom
State/province [91] 0 0
London
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Taunton
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
pharmaand GmbH
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Foundation Medicine
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.
Trial website
https://clinicaltrials.gov/study/NCT02975934
Trial related presentations / publications
Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH; TRITON3 Investigators. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. doi: 10.1056/NEJMoa2214676. Epub 2023 Feb 16.
Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02975934