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

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 2

Locations

Brazil

Study Type

Interventional

Intervention

Goserelin

Prednisone

Abiraterone

Apalutamide

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Neoadjuvant therapy, High-risk Prostate Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept 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.

Sites / Locations

Instituto do Cancer do Estado de Sao Paulo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

ADT and Abiraterone

ADT, Abiraterone and Apalutamide

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Residual cellularity rate

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

Pathologic downgrading

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

PSA decline rate

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

Rate of positive surgical margins

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

Rate of undetectable PSA

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

Rate of Grade ≥ 3 CTCAE adverse events

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

Full Information

NCT ID

NCT02789878

First Posted

May 25, 2016

Last Updated

September 14, 2022

Sponsor

Instituto do Cancer do Estado de São Paulo

Collaborators

Janssen, LP

1. Study Identification

Unique Protocol Identification Number

NCT02789878

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

January 24, 2019 (Actual)

Primary Completion Date

April 30, 2022 (Actual)

Study Completion Date

August 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Instituto do Cancer do Estado de São Paulo

Collaborators

Janssen, LP

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Neoadjuvant therapy, High-risk Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ADT and Abiraterone

Arm Type

Experimental

Arm Description

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.

Arm Title

ADT, Abiraterone and Apalutamide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Goserelin

Other Intervention Name(s)

ADT

Intervention Description

Androgen Deprivation Therapy

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

Corticosteroid

Intervention Type

Drug

Intervention Name(s)

Abiraterone

Other Intervention Name(s)

Zytiga

Intervention Description

CYP17 inhibitor

Intervention Type

Drug

Intervention Name(s)

Apalutamide

Other Intervention Name(s)

ARN-509

Intervention Description

Androgen-receptor antagonist

Primary Outcome Measure Information:

Title

Pathologic response

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Residual cellularity rate

Description

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

Time Frame

3 months

Title

Pathologic downgrading

Description

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

Time Frame

3 months

Title

PSA decline rate

Description

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

Time Frame

3 months

Title

Rate of positive surgical margins

Description

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

Time Frame

3 months

Title

Rate of undetectable PSA

Description

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

Time Frame

12 months

Title

Rate of Grade ≥ 3 CTCAE adverse events

Description

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

Time Frame

3 months

Other Pre-specified Outcome Measures:

Title

Rate of Magnetic Resonance Image Downstaging after Neoadjuvant Therapy

Description

To compare the MR image downstaging after neoadjuvant therapy with pathologic analysis of the prostatectomy specimen

Time Frame

3 months

Title

Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response.

Description

To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.

Time Frame

3 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Diogo A Bastos, MD

Organizational Affiliation

Instituto do Cancer do Estado de São Paulo

Official's Role

Principal Investigator

Facility Information:

Facility Name

Instituto do Cancer do Estado de Sao Paulo

City

Sao Paulo

State/Province

ZIP/Postal Code

01246-0000

Country

Brazil

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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