Clinical trial NCT02789878: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Neoadjuvant therapy
High-risk Prostate Cancer
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
Collaborators: name: Janssen, LP
First posted: 2016-06-03
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Pathologic response
timeFrame: 3 months
Secondary outcomes:
measure: Residual cellularity rate
timeFrame: 3 months
measure: Pathologic downgrading
timeFrame: 3 months
measure: PSA decline rate
timeFrame: 3 months
measure: Rate of positive surgical margins
timeFrame: 3 months
measure: Rate of undetectable PSA
timeFrame: 12 months
measure: Rate of Grade ≥ 3 CTCAE adverse events
timeFrame: 3 months
Other outcomes:
measure: Rate of Magnetic Resonance Image Downstaging after Neoadjuvant Therapy
timeFrame: 3 months
measure: Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response.
timeFrame: 3 months
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
state: SP
Study officials:
affiliation: Instituto do Cancer do Estado de São Paulo
name: Diogo A Bastos, MD
role: PRINCIPAL_INVESTIGATOR
References: