Clinical Trials /

Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for High-Risk Prostate Cancer

NCT02789878

Description:

This is a randomized study to evaluate the efficacy and safety neoadjuvant androgen deprivation therapy with goserelin and abiraterone with or without apalutamide prior to radical prostatectomy for patients diagnosed with localized high-risk prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for High-Risk Prostate Cancer
  • Official Title: Phase II Study of Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for Patients With High-Risk Localized Prostate Cancer Prior to Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: NP 779/15
  • NCT ID: NCT02789878

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
GoserelinADTADT and Abiraterone
PrednisoneADT and Abiraterone
AbirateroneZytigaADT and Abiraterone
ApalutamideARN-509ADT, Abiraterone and Apalutamide

Purpose

This is a randomized study to evaluate the efficacy and safety neoadjuvant androgen deprivation therapy with goserelin and abiraterone with or without apalutamide prior to radical prostatectomy for patients diagnosed with localized high-risk prostate cancer.

Detailed Description

      In the prostate specific antigen (PSA) era, about 15% to 20% of patients are diagnosed with
      high-risk localized disease and radical prostatectomy is a standard therapy for this subgroup
      of patients. However, despite best local therapy, about 30-60% of high-risk patients will
      eventually develop biochemical relapse and a significant proportion of these patients may
      progress with metastatic disease and die from prostate cancer. Currently, there is no data
      supporting the use of neoadjuvant therapy for patients with high-risk disease since studies
      failed to demonstrate clinically significant benefit with standard androgen deprivation
      therapy (ADT). Following improved outcomes in other malignancies with the use of neoadjuvant
      therapy with active drugs in the metastatic setting, there is a growing interest in
      evaluating new-generation androgen receptor (AR)-targeted therapy in earlier stages of
      prostate cancer. Therefore, the goal of this study is to evaluate the efficacy and safety of
      neoadjuvant therapy with ADT and abiraterone versus maximal androgen blockade using ADT,
      abiraterone and apalutamide for patients with high-risk localized prostate cancer.
    

Trial Arms

NameTypeDescriptionInterventions
ADT and AbirateroneExperimentalGoserelin 10.8 mg, single dose, subcutaneously. Abiraterone 1,000 mg, once daily, orally for 3 months. Prednisone 5 mg, once daily, orally for 3 months.
  • Goserelin
  • Prednisone
  • Abiraterone
ADT, Abiraterone and ApalutamideExperimentalGoserelin 10.8 mg, single dose, subcutaneously. Abiraterone 1,000 mg, once daily, orally for 3 months. Prednisone 5 mg, once daily, orally for 3 months. Apalutamide 240 mg, once daily, orally for 3 months.
  • Goserelin
  • Prednisone
  • Abiraterone
  • Apalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic confirmed prostatic adenocarcinoma

          -  Non-castrate levels of testosterone (> 150 ng/dL)

          -  High-risk localized prostate cancer, defined by either:

               -  Tumor stage T3 by digital rectal examination, or

               -  Primary tumor Gleason score ≥ 8, or

               -  PSA ≥ 20 ng/mL

          -  Willing to undergo prostatectomy as primary treatment for localized prostate cancer

          -  Adequate hematologic, renal and hepatic function:

               -  WBC > 3000/uL

               -  Platelets > 150,000/uL

               -  Creatinine < 2 mg/dL

               -  Bilirubin < 1.5 x upper limit of normal (ULN)

               -  AST/ALT < 2 x ULN

          -  Karnofsky Performance Status (KPS) ≥ 80%

          -  Able to swallow the study drugs whole as tablets

        Exclusion Criteria:

          -  Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of
             the prostate

          -  Current or prior hormonal therapy, radiation therapy or chemotherapy for prostate
             cancer

          -  Evidence of metastatic disease (M1) on imaging studies

          -  Other prior malignancy less than or equal to 5 years prior to randomization with the
             exception of squamous or basal cell skin carcinoma

          -  Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III
             or IV heart failure

          -  History of prior cardiac arrhythmia.

          -  Evidence of serious and/or unstable pre-existing medical, psychiatric or other
             condition (including laboratory abnormalities) that could interfere with patient
             safety or provision of informed consent to participate in this study.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic response
Time Frame:3 months
Safety Issue:
Description:To compare the rate of pathologic complete response (pCR) or pathologic near complete response (pnCR), defined as less than 0,5 cm of residual tumor in the prostatectomy specimen after neoadjuvant therapy.

Secondary Outcome Measures

Measure:Residual cellularity rate
Time Frame:3 months
Safety Issue:
Description:To compare the rate of residual cellularity ≤ 30% in the prostatectomy specimen after neoadjuvant therapy.
Measure:Pathologic downgrading
Time Frame:3 months
Safety Issue:
Description:To compare the rate of pathologic downgrading to ≤ ypT2N0 in the prostatectomy specimen after neoadjuvant therapy.
Measure:PSA decline rate
Time Frame:3 months
Safety Issue:
Description:To compare the rate of PSA decline ≥ 50% and 90% after 3 months of neoadjuvant therapy.
Measure:Rate of positive surgical margins
Time Frame:3 months
Safety Issue:
Description:To compare the rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.
Measure:Rate of undetectable PSA
Time Frame:12 months
Safety Issue:
Description:To compare the rate of patients with undetectable PSA 12 months after radical prostatectomy.
Measure:Rate of Grade ≥ 3 CTCAE adverse events
Time Frame:3 months
Safety Issue:
Description:To compare the rate of CTCAE grade 3 or higher adverse events of the neoadjuvant therapy arms

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Instituto do Cancer do Estado de São Paulo

Trial Keywords

  • Neoadjuvant therapy
  • High-risk Prostate Cancer

Last Updated

February 12, 2020