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

Phase 2

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: Goserelin; Drug: Prednisone; Drug: Abiraterone; Drug: Apalutamide

• Registration Number: NCT02789878
• Lead Sponsor: Instituto do Cancer do Estado de São Paulo

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.

Study Timeline

• Study First Submitted: 2016-05-25
• Study First Submitted QC: 2016-06-02
• Study First Posted: 2016-06-03
• Study Start: 2019-01-24
• Primary Completion: 2022-04-30
• Study Completion: 2022-08-01
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-14
• Last Update Posted: 2022-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 64

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ADT and Abiraterone	Goserelin	* 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.
ADT and Abiraterone	Prednisone	* 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.
ADT and Abiraterone	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.
ADT, Abiraterone and Apalutamide	Goserelin	* 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.
ADT, Abiraterone and Apalutamide	Prednisone	* 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.
ADT, Abiraterone and Apalutamide	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.
ADT, Abiraterone and Apalutamide	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. * Apalutamide 240 mg, once daily, orally for 3 months.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Residual cellularity rate	3 months	To compare the rate of residual cellularity ≤ 30% 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 positive surgical margins	3 months	To compare the rate of positive surgical margins 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.

Trial Locations

Locations (1)

Instituto do Cancer do Estado de Sao Paulo; 🇧🇷 Sao Paulo, SP, Brazil