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

Prostate Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02789878
• Other study ID #: NP 779/15
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2019
• Est. completion date: August 1, 2022

Study information

• Verified date: September 2022
• Source: Instituto do Cancer do Estado de São Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 1, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Goserelin
Androgen Deprivation Therapy
• Prednisone
Corticosteroid
• Abiraterone
CYP17 inhibitor
• Apalutamide
Androgen-receptor antagonist

Locations

Country	Name	City	State
Brazil	Instituto do Cancer do Estado de Sao Paulo	Sao Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
Instituto do Cancer do Estado de São Paulo	Janssen, LP

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of Magnetic Resonance Image Downstaging after Neoadjuvant Therapy	To compare the MR image downstaging after neoadjuvant therapy with pathologic analysis of the prostatectomy specimen	3 months
Other	Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response.	To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.	3 months
Primary	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.	3 months
Secondary	Residual cellularity rate	To compare the rate of residual cellularity = 30% in the prostatectomy specimen after neoadjuvant therapy.	3 months
Secondary	Pathologic downgrading	To compare the rate of pathologic downgrading to = ypT2N0 in the prostatectomy specimen after neoadjuvant therapy.	3 months
Secondary	PSA decline rate	To compare the rate of PSA decline = 50% and 90% after 3 months of neoadjuvant therapy.	3 months
Secondary	Rate of positive surgical margins	To compare the rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.	3 months
Secondary	Rate of undetectable PSA	To compare the rate of patients with undetectable PSA 12 months after radical prostatectomy.	12 months
Secondary	Rate of Grade = 3 CTCAE adverse events	To compare the rate of CTCAE grade 3 or higher adverse events of the neoadjuvant therapy arms	3 months