Clinical Trials /

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

NCT03767244

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Apalutamide in Participants With High‑Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CR108535
  • SECONDARY ID: 56021927PCR3011
  • SECONDARY ID: 2018‐001746‐34
  • SECONDARY ID: 2018-001746-34
  • NCT ID: NCT03767244

Conditions

  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
ApalutamideJNJ-56021927ADT + Apalutamide
Androgen Deprivation Therapy (ADT)ADT + Apalutamide
PlaceboADT + Placebo

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
ADT + ApalutamideExperimentalParticipants 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.
  • Apalutamide
  • Androgen Deprivation Therapy (ADT)
ADT + PlaceboExperimentalParticipants 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 radical prostatectomy, followed by an additional six cycles of placebo treatment.
  • Androgen Deprivation Therapy (ADT)
  • Placebo

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Pathologic complete response (pCR)
Time Frame:Approximately 4 years
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Prostate Specific Antigen (PSA)-Free Survival
Time Frame:Approximately 4 years
Safety Issue:
Description: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.
Measure:Progression-Free Survival (PFS)
Time Frame:Approximately 8 years
Safety Issue:
Description: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.
Measure:Number of Participants with Adverse Events
Time Frame:Up to 30 days after last dose of study drug (Approximately 8 years)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
Measure:Number of Participants with Treatment Compliance Rate
Time Frame:Up to 30 days after last dose of study drug (Approximately 8 years)
Safety Issue:
Description:Number of participants who are complaint with study treatment will be assessed.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

November 14, 2019