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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02789878

Enrollment

Registered

2016-06-03

Start date

2019-01-24

Completion date

2022-08-01

Last updated

2022-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Keywords

Neoadjuvant therapy, High-risk Prostate Cancer

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.

Interventions

DRUGGoserelin

Androgen Deprivation Therapy

DRUGPrednisone

Corticosteroid

DRUGAbiraterone

CYP17 inhibitor

DRUGApalutamide

Androgen-receptor antagonist

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

MALE

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Pathologic response	3 months	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

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

Other

Measure	Time frame	Description
Rate of Magnetic Resonance Image Downstaging after Neoadjuvant Therapy	3 months	To compare the MR image downstaging after neoadjuvant therapy with pathologic analysis of the prostatectomy specimen
Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response.	3 months	To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.

Countries

Brazil

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: May 29, 2026