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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02789878
Recruitment Status : Recruiting
First Posted : June 3, 2016
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Goserelin Drug: Prednisone Drug: Abiraterone Drug: Apalutamide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: ADT and 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.
Drug: Goserelin
Androgen Deprivation Therapy
Other Name: ADT

Drug: Prednisone
Corticosteroid

Drug: Abiraterone
CYP17 inhibitor
Other Name: Zytiga

Experimental: ADT, Abiraterone and 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.
Drug: Goserelin
Androgen Deprivation Therapy
Other Name: ADT

Drug: Prednisone
Corticosteroid

Drug: Abiraterone
CYP17 inhibitor
Other Name: Zytiga

Drug: Apalutamide
Androgen-receptor antagonist
Other Name: ARN-509




Primary Outcome Measures :
  1. Pathologic response [ Time Frame: 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 :
  1. Residual cellularity rate [ Time Frame: 3 months ]
    To compare the rate of residual cellularity ≤ 30% in the prostatectomy specimen after neoadjuvant therapy.

  2. Pathologic downgrading [ Time Frame: 3 months ]
    To compare the rate of pathologic downgrading to ≤ ypT2N0 in the prostatectomy specimen after neoadjuvant therapy.

  3. PSA decline rate [ Time Frame: 3 months ]
    To compare the rate of PSA decline ≥ 50% and 90% after 3 months of neoadjuvant therapy.

  4. Rate of positive surgical margins [ Time Frame: 3 months ]
    To compare the rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.

  5. Rate of undetectable PSA [ Time Frame: 12 months ]
    To compare the rate of patients with undetectable PSA 12 months after radical prostatectomy.

  6. Rate of Grade ≥ 3 CTCAE adverse events [ Time Frame: 3 months ]
    To compare the rate of CTCAE grade 3 or higher adverse events of the neoadjuvant therapy arms


Other Outcome Measures:
  1. Rate of Magnetic Resonance Image Downstaging after Neoadjuvant Therapy [ Time Frame: 3 months ]
    To compare the MR image downstaging after neoadjuvant therapy with pathologic analysis of the prostatectomy specimen

  2. Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response. [ Time Frame: 3 months ]
    To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02789878


Contacts
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Contact: Diogo A Bastos, MD +55 11 38932691 diogo.bastos@hc.fm.usp.br
Contact: Mariana Fiuza +55 11 38932691 mariana.fiuza@hc.fm.usp.br

Locations
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Brazil
Instituto do Cancer do Estado de Sao Paulo Recruiting
Sao Paulo, SP, Brazil, 01246-0000
Contact: Roberto Arai    +55 11 38932619    roberto.arai@hc.fm.usp.br   
Contact: Suleima A Jokh    +55 11 38932617    suleima.jokh@hc.fm.usp.br   
Principal Investigator: Diogo Bastos, MD         
Sub-Investigator: Rafael Coelho, MD         
Sub-Investigator: David Muniz, MD         
Sub-Investigator: Jamile Silva, MD         
Sub-Investigator: Natalia Fraile, MD         
Sub-Investigator: Giuliano Guglielmetti, MD         
Sub-Investigator: Mauricio Cordeiro, MD         
Sub-Investigator: Paulo Afonso Carvalho, MD         
Sub-Investigator: Arnaldo Fazoli, MD         
Sub-Investigator: Sheila Faraj, MD         
Sub-Investigator: William Nahas, MD         
Sponsors and Collaborators
Instituto do Cancer do Estado de São Paulo
Janssen, LP
Investigators
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Principal Investigator: Diogo A Bastos, MD Instituto do Cancer do Estado de São Paulo
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Responsible Party: Instituto do Cancer do Estado de São Paulo
ClinicalTrials.gov Identifier: NCT02789878    
Other Study ID Numbers: NP 779/15
First Posted: June 3, 2016    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Instituto do Cancer do Estado de São Paulo:
Neoadjuvant therapy
High-risk Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Goserelin
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents