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

NCT ID: NCT02789878

Last Updated: 2022-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-24
• Study Completion Date: 2022-08-01

Brief Summary

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ADT and Abiraterone

• Goserelin 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.

Group Type: EXPERIMENTAL

Goserelin

Intervention Type: DRUG

Androgen Deprivation Therapy

Prednisone

Intervention Type: DRUG

Corticosteroid

Abiraterone

Intervention Type: DRUG

CYP17 inhibitor

ADT, Abiraterone and Apalutamide

• Goserelin 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.

Group Type: EXPERIMENTAL

Goserelin

Intervention Type: DRUG

Androgen Deprivation Therapy

Prednisone

Intervention Type: DRUG

Corticosteroid

Abiraterone

Intervention Type: DRUG

CYP17 inhibitor

Apalutamide

Intervention Type: DRUG

Androgen-receptor antagonist

Interventions

Goserelin

Androgen Deprivation Therapy

Intervention Type: DRUG

Prednisone

Corticosteroid

Intervention Type: DRUG

Abiraterone

CYP17 inhibitor

Intervention Type: DRUG

Apalutamide

Androgen-receptor antagonist

Intervention Type: DRUG

Other Intervention Names

ADT; Zytiga; ARN-509

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen, LP

INDUSTRY

Sponsor Role: collaborator

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Diogo A Bastos, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Cancer do Estado de São Paulo

Locations

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

NP 779/15

Identifier Type: -

Identifier Source: org_study_id