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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 : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to determine if treatment with androgen deprivation therapy (ADT) plus apalutamide before and after radical prostatectomy 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 ADT plus placebo.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Apalutamide Drug: Androgen Deprivation Therapy (ADT) Drug: Placebo Phase 3

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 radical prostatectomy. It is hypothesized that androgen blockade prior to and after radical prostatectomy 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 radical prostatectomy 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 (up to 12 months) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : April 22, 2024
Estimated Study Completion Date : December 28, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: ADT + Apalutamide
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, followed by an additional six cycles of treatment.
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]).

Experimental: ADT + Placebo
Participants will receive ADT with oral administration of matching placebo treatment.
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.




Primary Outcome Measures :
  1. Percentage of Participants with Pathologic complete response (pCR) [ Time Frame: Approximately 4 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).

  2. Metastasis-Free Survival (MFS) [ Time Frame: Approximately 8 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.


Secondary Outcome Measures :
  1. Prostate Specific Antigen (PSA)-Free Survival [ Time Frame: Approximately 4 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • Candidate for radical prostatectomy with lymph node dissection as per the investigator
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • Contraceptive (birth control) use by men (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
  • Able to receive androgen deprivation therapy (ADT) for up to 1 year, per the investigator's assessment

Exclusion Criteria:

  • Distant metastasis (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
  • Prior treatment with antiandrogen
  • History of 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767244


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03767244     History of Changes
Other Study ID Numbers: CR108535
56021927PCR3011 ( Other Identifier: Janssen Research & Development, LLC )
2018‐001746‐34 ( EudraCT Number )
2018-001746-34 ( EudraCT Number )
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs