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

Instituto do Cancer do Estado de São Paulo64 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Prostate Cancer

Interventions

GoserelinDRUG

Androgen Deprivation Therapy

PrednisoneDRUG

Corticosteroid

AbirateroneDRUG

CYP17 inhibitor

Apalutamide

Eligibility

Sex: MALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (1)

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Outcomes

Primary Outcomes

Pathologic response

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.

Time frame: 3 months

Secondary Outcomes

Residual cellularity rate

To compare the rate of residual cellularity ≤ 30% in the prostatectomy specimen after neoadjuvant therapy.

Time frame: 3 months

Pathologic downgrading

To compare the rate of pathologic downgrading to ≤ ypT2N0 in the prostatectomy specimen after neoadjuvant therapy.

Time frame: 3 months

PSA decline rate

To compare the rate of PSA decline ≥ 50% and 90% after 3 months of neoadjuvant therapy.

Time frame: 3 months

Rate of positive surgical margins

To compare the rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.

Time frame: 3 months

Rate of undetectable PSA

To compare the rate of patients with undetectable PSA 12 months after radical prostatectomy.

Time frame: 12 months

Rate of Grade ≥ 3 CTCAE adverse events

To compare the rate of CTCAE grade 3 or higher adverse events of the neoadjuvant therapy arms

Time frame: 3 months

Data from ClinicalTrials.gov

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