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A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy (PROTEUS)

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ClinicalTrials.gov Identifier: NCT03767244
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : September 28, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE December 5, 2018
First Posted Date  ICMJE December 6, 2018
Last Update Posted Date September 28, 2022
Actual Study Start Date  ICMJE June 11, 2019
Estimated Primary Completion Date April 22, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2022)
  • Percentage of Participants with Pathologic complete response (pCR) [ Time Frame: Approximately 4 years ]
    pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
  • Metastasis-Free Survival (MFS) [ Time Frame: Up to 7 years and 5 months ]
    MFS is defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • Percentage of Participants with Pathologic complete response (pCR) [ Time Frame: Approximately 3.5 years ]
    pCR is defined as no residual tumor detected in the prostatectomy specimen both by hematoxylin and eosin (H&E) staining and ancillary immunohistochemistry (IHC) as needed, as assessed by a pathology blinded independent central radiology review (BICR).
  • Metastasis-Free Survival (MFS) [ Time Frame: Approximately 5 years ]
    MFS is defined as the time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2022)
  • Prostate Specific Antigen (PSA)-Free Survival [ Time Frame: Approximately 4 years ]
    PSA-free survival with testosterone recovery defined as the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with pelvic lymph node dissection or death, whichever occurs first.
  • Event Free Survival (EFS) [ Time Frame: Up to 7 years and 5 months ]
    EFS defined as time from randomization to any of the following events: biochemical failure (BCF); or local or regional recurrence by BICR or histopathological assessment; or distant metastasis by BICR or histopathological assessment; or death.
  • Time to Subsequent First Treatments (TTST-1) [ Time Frame: Up to 7 years and 5 months ]
    TTST-1 is defined as the time from randomization to the date of first subsequent therapy.
  • Time to Distant Metastasis (TTDM) [ Time Frame: Up to 7 years and 5 months ]
    TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.
  • MFS Based on Conventional Imaging [ Time Frame: Up to 7 years and 5 months ]
    MFS based on conventional imaging, defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on CT/MRI and bone scan by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
  • Number of Participants with Adverse Events [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
  • Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Number of participants with vital signs (including body temperature, heart rate, respiratory rate, and blood pressure) abnormalities will be reported.
  • Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Number of participants with physical examinations (including general appearance of the participant, height, weight, and examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, musculoskeletal system, lymphatic system, and nervous system) abnormalities will be reported.
  • Number of Participants with Treatment Compliance Rate [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Number of participants who are complaint with study treatment will be assessed.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • Prostate Specific Antigen (PSA)-Free Survival [ Time Frame: Approximately 8 years ]
    PSA-free survival with testosterone recovery (within normal limits) defined as the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with lymph node dissection (RPLND) or death, whichever occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 8 years ]
    PFS is defined as the time from randomization to first documentation of BICR confirmed radiographic progressive disease or death due to any cause (whichever occurs first) plus 1 day. Progressive disease will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. As per RECIST v1.1, for participants with at least 1 measurable lesion, disease progression will be defined as at least a 20 percent (%) increase in the sum of diameters of target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For participants with only non-measurable disease observed on computed tomography (CT) or magnetic resonance imaging (MRI) scans, unequivocal progression or the appearance of one or more new lesions will be considered progression. For new bone lesions detected on bone scans, a second imaging modality will be required to confirm progression.
  • Number of Participants with Adverse Events [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
  • Number of Participants with Treatment Compliance Rate [ Time Frame: Up to 30 days after last dose of study drug (Approximately 8 years) ]
    Number of participants who are complaint with study treatment will be assessed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Official Title  ICMJE 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
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.
Detailed Description High-risk prostate cancer accounts for approximately 15 percent (%) of newly diagnosed prostate cancers. A systemic therapy that eradicates micrometastatic disease is needed to improve survival in high-risk participants undergoing RP with pLND. It is hypothesized that androgen blockade prior to and after RP with pLND may improve outcomes for participants at the highest risk for recurrence. This study is designed to evaluate if androgen blockade administered prior to and after RP with pLND will increase the rate of pathological complete response (pCR) and lead to better overall outcomes. ERLEADA (apalutamide, also known as JNJ-56021927 and ARN-509) is an orally available, non-steroidal small molecule, which acts as a potent and selective antagonist of the androgen receptor (AR), currently being developed for the treatment of prostate cancer. The study includes screening phase (approximately up to 35 days before randomization), treatment phase (the planned Treatment Phase will include a total of 12 treatment cycles of apalutamide or placebo; 6 cycles prior to RP with pLND (Cycle 1 through Cycle 6) and 6 cycles after RP with pLND (Cycle 7 through Cycle 12). Cycle 1 Day 1 will start within 3 days after randomization) and follow-up phase. The end of study (study completion) is defined as last participant assessment at study site with approximate study duration of 8 years. Participants will undergo efficacy, pharmacokinetics and biomarker evaluations. The safety will be monitored throughout the study. An open-label sub-study comparing apalutamide plus ADT before and after RP with pLND with standard of care treatment will be initiated at selected sites upon notification by the sponsor.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE
  • Drug: Apalutamide
    Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
    Other Name: JNJ-56021927
  • Drug: 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]).
  • Drug: Placebo
    Participants will receive matching placebo oral tablets daily.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Apalutamide
    • Drug: Androgen Deprivation Therapy (ADT)
  • 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.
    Interventions:
    • Drug: Androgen Deprivation Therapy (ADT)
    • Drug: Placebo
Publications * Ravi P, Kwak L, Xie W, Kelleher K, Acosta AM, McKay RR, Kibel AS, Taplin ME. Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis. J Urol. 2022 Oct;208(4):838-845. doi: 10.1097/JU.0000000000002803. Epub 2022 Sep 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 27, 2022)
2500
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2018)
1500
Estimated Study Completion Date  ICMJE April 7, 2027
Estimated Primary Completion Date April 22, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 Participate-In-This-Study@its.jnj.com
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Czechia,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries China
 
Administrative Information
NCT Number  ICMJE NCT03767244
Other Study ID Numbers  ICMJE CR108535
56021927PCR3011 ( Other Identifier: Janssen Research & Development, LLC )
2018-001746-34 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

The data sharing policy of the Janssen Pharmaceutical companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

URL: https://www.janssen.com/clinical-trials/transparency
Current Responsible Party Janssen Research & Development, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Janssen Research & Development, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP