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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03767244




Registration number
NCT03767244
Ethics application status
Date submitted
5/12/2018
Date registered
6/12/2018
Date last updated
23/05/2024

Titles & IDs
Public title
A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Scientific title
A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Secondary ID [1] 0 0
56021927PCR3011
Secondary ID [2] 0 0
CR108535
Universal Trial Number (UTN)
Trial acronym
PROTEUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Apalutamide
Treatment: Drugs - Androgen Deprivation Therapy (ADT)
Treatment: Drugs - Placebo

Experimental: Apalutamide + ADT - Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment.

Experimental: Placebo + ADT - Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment.


Treatment: Drugs: Apalutamide
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.

Treatment: Drugs: Androgen Deprivation Therapy (ADT)
Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter [ng/dL]).

Treatment: Drugs: Placebo
Participants will receive matching placebo oral tablets daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Pathologic complete response (pCR)
Timepoint [1] 0 0
Approximately 4 years
Primary outcome [2] 0 0
Metastasis-Free Survival (MFS)
Timepoint [2] 0 0
Up to 7 years and 5 months
Secondary outcome [1] 0 0
Prostate Specific Antigen (PSA)-Free Survival
Timepoint [1] 0 0
Approximately 4 years
Secondary outcome [2] 0 0
Event Free Survival (EFS)
Timepoint [2] 0 0
Up to 7 years and 5 months
Secondary outcome [3] 0 0
Time to Subsequent First Treatments (TTST-1)
Timepoint [3] 0 0
Up to 7 years and 5 months
Secondary outcome [4] 0 0
Time to Distant Metastasis (TTDM)
Timepoint [4] 0 0
Up to 7 years and 5 months
Secondary outcome [5] 0 0
MFS Based on Conventional Imaging
Timepoint [5] 0 0
Up to 7 years and 5 months
Secondary outcome [6] 0 0
Number of Participants with No Evidence of Disease (NED) at 4 Years
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability
Timepoint [7] 0 0
Up to 30 days after last dose of study drug (Approximately 8 years)
Secondary outcome [8] 0 0
Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability
Timepoint [8] 0 0
Up to 30 days after last dose of study drug (Approximately 8 years)
Secondary outcome [9] 0 0
Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability
Timepoint [9] 0 0
Up to 30 days after last dose of study drug (Approximately 8 years)
Secondary outcome [10] 0 0
Number of Participants with Treatment Compliance Rate
Timepoint [10] 0 0
Up to 30 days after last dose of study drug (Approximately 8 years)

Eligibility
Key inclusion criteria
- Histologically confirmed adenocarcinoma of the prostate

- High-risk disease defined by a total Gleason Sum Score greater than equal to (>=) 4+3
(=Grade Groups [GG] 3 5) and >=1 of the following 4 criteria: a) Any combination of
Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores
(with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason
Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and
Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or
5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted
core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8
(=GG 4), each with > 80 percent (%) involvement

- Candidate for radical prostatectomy with pelvic lymph node dissection as per the
investigator

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

- Contraceptive use by male participants (and female partners of male participants
enrolled in the study who are of childbearing potential or are pregnant) should be
consistent with local regulations regarding the use of contraceptive methods for
participants participating in clinical studies

- Able to receive androgen deprivation therapy (ADT) for at least 13 months
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease
below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of
distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal
disease (clinical N stage; N1 versus N0) will be assessed by central radiological
review. Participants are considered eligible only if the central radiological review
confirms clinical stage M0

- (a) Prior treatment with androgen receptor antagonists; (b) Treatment with
gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF)
signature

- History of prior systemic or local therapy for prostate cancer, including pelvic
radiation for prostate cancer

- Use of any investigational agent less than or equals to (<=)4 weeks prior to
randomization or any therapeutic procedure for prostate cancer at any time

- Major surgery <=4 weeks prior to randomization

- Any of the following within 12 months prior to first dose of study drug: severe or
unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial
or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated
deep vein thrombosis is not considered exclusionary

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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
11/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/07/2029
Actual
Sample size
Target
Accrual to date
Final
2517
Recruitment in Australia
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Epworth Eastern Hospital - Box Hill
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St. Vincent's Hospital Sydney - Darlinghurst
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Austin Health - Heidelberg
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Australian Urology Associates Pty Ltd - Malvern
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Royal Melbourne Hospital - Parkville
Recruitment hospital [6] 0 0
Northern Cancer Institute - St Leonards
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Australian Clinical Trials - SAN Clinic - Wahroonga
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Westmead Hospital - Westmead
Recruitment hospital [9] 0 0
Princess Alexandra Hospital - Woolloongabba
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3128q - Box Hill
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2010 - Darlinghurst
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3084 - Heidelberg
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3144 - Malvern
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3052 - Parkville
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2065 - St Leonards
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2076 - Wahroonga
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2145 - Westmead
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4102 - Woolloongabba
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine if treatment with apalutamide plus androgen
deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node
dissection (pLND) in participants with high-risk localized or locally advanced prostate
cancer results in an improvement in pathological complete response (pCR) rate and
metastasis-free survival (MFS) as compared to placebo plus ADT.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03767244
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
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