This multicenter randomized phase II trial investigates the impact of intense androgen deprivation on radical prostatectomy (RP) pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).
This is a multicenter, phase II, prospective, randomized trial designed to investigate the efficacy of neoadjuvant and adjuvant abiraterone acetate + apalutamide for men with intermediate-high risk prostate cancer who are candidates for RP. The study includes two parts. In part 1, patients will be randomized in 1:1 ratio to receive 6 months of abiraterone acetate, apalutamide, leuprolide and prednisone (Arm 1A) versus 6 months of abiraterone acetate, leuprolide and prednisone (Arm 1B) followed by RP, stratified by risk factor (intermediate versus high-risk). High-risk factors will be defined as a Gleason score ≥ 8, PSA \> 20 ng/dL, or T3 disease on MRI. In part 2 (post-RP), patients will be randomized in 1:1 ratio to receive an additional 12 months of abiraterone acetate, apalutamide, leuprolide and prednisone (Arm 2A) or observation (Arm 2B) stratified by type of neoadjuvant therapy and pathological T-stage (\< pT3 versus ≥ pT3) after RP but before cycle 7 day 1 following neoadjuvant therapy. There will be an early stopping rule for Part 2 should a high rate of patients refuse to participate or drop out early while receiving adjuvant therapy (\<6 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
118
University of California, San Diego Moores Cancer Center
La Jolla, California, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Combined pCR or MRD Rate [Part 1]
Pathological response, defined as achieving either pCR or MRD at radical prostatectomy (RP). Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen. MRD will be defined as residual tumor in the RP specimen measuring ≤ 5 mm.
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2]
3-year bPFS rate is defined as the probability of biochemical progression free and survival at 3 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 3-year mark are censored at date last disease evaluation.
Time frame: At 3 years post RP
Rate of pCR at RP (Part 1)
Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen at radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Median of Residual Cancer Burden (RCB) at RP (Part 1)
RCB was calculated as "tumor volume (cm\^3) X % cellularity". RCB was analyzed as a continuous score (with median and range) instead of a categorical variable based on the percentile cutoff point, at the time of radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Cribriform at RP (Part 1)
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Presence or cribriform was evaluated by central pathology review of specimens at radical prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Intraductal Carcinoma at RP (Part 1)
Intraductal carcinoma was evaluated by central pathology review of specimens at Radical Prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Positive Surgical Margins at RP (Part 1)
Pathologic specimens were centrally reviewed and counted for positive surgical margins at the time of Radical Prostatectomy (RP).
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1)
Prostate specific antigen (PSA) was measured on day 1 of each cycle during the neoadjuvant therapy. PSA nadir was defined as the lowest PSA value prior to Radical Prostatectomy (RP). Number and percent of participants with nadir PSA \< 0.2 ng/mL were reported.
Time frame: Assessed on day 1 of each cycle (1 cycle=28 +/- 2 days), up to 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Intra-operative Complications Following RP (Part 1)
Intra-operative complications were collected via questionnaire following Radical Prostatectomy.
Time frame: Assessed post-RP, at 6 months from the initiation of neoadjuvant therapy.
Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2]
2-year bPFS rate is defined as the probability of biochemical progression free and survival at 2 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 2-year mark are censored at date of last disease evaluation.
Time frame: At 2 years post RP
Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2]
4-year bPFS rate is defined as the probability of biochemical progression free and survival at 4 years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event is considered to be biochemical progression (defined as a confirmed PSA ≥ 0.2 ng/mL), local, regional, or distant metastatic disease on CT/MRI or bone scan, or receipt of post-operative systemic therapy or radiotherapy for rising PSA, or death from any cause. Participants who are lost to follow-up before the 4-year mark are censored at date of last disease evaluation.
Time frame: At 4 years post RP
Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 2-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 2-year mark are censored at date of last follow-up.
Time frame: At 2-years post RP
Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 3-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 3-year mark are censored at date of last follow-up.
Time frame: At 3 years post RP
Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2)
Defined as the probability of freedom from further anti-cancer therapy at 4-years from the date of Part 2 randomization, which is estimated using Kaplan Meier methods. The event includes initiation of anti-cancer therapy (radiation therapy, ADT, or other therapies) for rising PSAs and/or clinical progression. Participants who are lost to follow-up before the 4-year mark are censored at date of last follow-up.
Time frame: At 4-years post RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 6-months post-RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 12-months post-RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2)
The QOL will be measured using the Expanded Prostate Cancer Index Composite 26 (EPIC-26). For part 2, the questionnaires will be administered at 6 months, 12 months, and 24 months post RP. Resulting domain scores for EPIC-26 (urinary incontinence, urinary obstruction, sexual, bowel, hormonal/vitality) is on a 0-100 scale, with higher values representing a more favorable health-related QOL.
Time frame: At 24-months post-RP