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NCT Number: NCT03767244

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Prostatic Neoplasms Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Aleman, Caba, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Apalutamide

Drug

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

Other names: JNJ-56021927

Androgen deprivation therapy (ADT)

Drug

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]).

Placebo

Drug

Participants will receive matching placebo oral tablets daily.

Primary outcomes

  1. 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.

  2. 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 occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Number of Participants with No Evidence of Disease (NED) at 4 Years

    Time frame: Up to 4 years

    Number of participants with NED at 4 years will be reported. NED at 4 years is defined as: (a) alive, (b) Undetectable prostate-specific antigen (PSA), (c) No distant metastasis, (d) No local or regional recurrence, (e) No subsequent therapy for prostate cancer, (f) Testosterone recovery to physiological testosterone levels, defined as 200 nanograms per deciliter (ng/dL).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study 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

Acronym: PROTEUS

Important dates

Study start
2019
Primary completion
2026
Study completion
2028
First posted
Dec 6, 2018
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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