Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02903368
Collaborator
Janssen Scientific Affairs, LLC (Industry)
118
Enrollment
4
Locations
4
Arms
91.4
Anticipated Duration (Months)
29.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

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 Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Randomized Study Of Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide For Intermediate-High Risk Prostate Cancer Undergoing Prostatectomy
Actual Study Start Date :
Oct 19, 2016
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm 1A: AAPL Neoadjuvant Therapy [Part 1]

Eligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 months Pts x weeks to RP

Drug: Apalutamide
Other Names:
  • JNJ-56021927
  • ARN-509
  • Drug: Leuprolide
    Other Names:
  • Lupron
  • Eligard
  • Drug: Prednisone
    Other Names:
  • Deltasone
  • Drug: Abiraterone Acetate
    Other Names:
  • Zytiga
  • Experimental: Arm 1B: APL Neoadjuvant Therapy [Part 1]

    Eligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months

    Drug: Leuprolide
    Other Names:
  • Lupron
  • Eligard
  • Drug: Prednisone
    Other Names:
  • Deltasone
  • Drug: Abiraterone Acetate
    Other Names:
  • Zytiga
  • Experimental: Arm 2A: AAPL Adjuvant Therapy [Part 2]

    Eligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 12 months

    Drug: Apalutamide
    Other Names:
  • JNJ-56021927
  • ARN-509
  • Drug: Leuprolide
    Other Names:
  • Lupron
  • Eligard
  • Drug: Prednisone
    Other Names:
  • Deltasone
  • Drug: Abiraterone Acetate
    Other Names:
  • Zytiga
  • No Intervention: Arm 2B: Observation [Part 2]

    Outcome Measures

    Primary Outcome Measures

    1. Combined pCR or MRD Rate [Part 1] [at 6 month]

      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.

    2. Median Biochemical Progression Free Survival (bPFS) [Part 2] [At 3 years post-RP]

      bPFS will be defined as the time from the date of randomization to the date of first evidence of disease progression (defined per protocol) or death from all causes, censored at the date of last disease follow-up.

    Secondary Outcome Measures

    1. Rate of pCR at RP [at 6 month]

      Pathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen at radical prostatectomy (RP).

    2. Median of Residual Cancer Burden (RCB) at RP [At 6 month]

      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).

    3. Percentage of Participants With Presenting Cribriform at RP [At RP (6 months)]

      Patients were 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 (Radical Prostatectomy). Cribriform at RP was evaluated by central pathology review at the completion of the study.

    4. Frequency of Presenting Intraductal Carcinoma at RP [At RP (6 months)]

      Patients were 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 (Radical Prostatectomy). Intraductal carcinoma at RP was evaluated by central pathology review at the completion of the study.

    5. Frequency of Positive Surgical Margins [At RP (6 months)]

      Pathologic specimens will be assessed and counted for positive surgical margins at the time of RP.

    6. Median Pre-RP PSA Nadir [At 6 months]

      prostate specific antigen (PSA) nadir defined as nadir PSA < 0.2 ng/mL

    7. Intra-operative and Post-operative Complications Following RP Between Treatment Arms (1A and 1B) [At 6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male ≥ 18 years of age.

    2. Histologically confirmed adenocarcinoma of the prostate without histological variants comprising >50% of the sample as determined by academic center central review (including neuroendocrine differentiation, small cell, sarcomatoid, ductal adenocarcinoma, squamous or transitional cell carcinoma).

    3. Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within seven months from screening. Less than 3 core biopsies are allowed if the patient has >1 cm or T3 disease on MRI.

    4. Patients must have the following features:

    • Gleason ≥ 4+3=7 OR

    • Gleason 3+4=7 AND at least one of the following: PSA >20 ng/dL or T3 disease (as determined by MRI).

    1. No evidence of metastatic disease as determined by radionuclide bone scans and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.

    2. Participants must be candidates for RP and considered surgically resectable by urologic evaluation.

    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

    4. Participants must have normal organ and marrow function as defined below:

    • Hemoglobin ≥ 9.0 g/dL

    • Absolute neutrophil count (ANC) ≥ 1,500/mcL

    • Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start

    • Serum potassium ≥ 3.5 mmol/L

    • Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible)

    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN

    • Serum albumin ≥ 3.0 g/dL

    • Serum creatinine < 2.0 x ULN

    • PTT≤60

    1. Participant must agree to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or must agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Participant must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.

    2. Medications known to lower the seizure threshold (see list under APPENDIX D: Representative Medications that May Predispose to Seizure) must be discontinued or substituted at least 1 week prior to study treatment.

    Exclusion Criteria:
    1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, Apalutamide and others), CYP17 inhibitors (including abiraterone acetate, TAK-700, galeterone, ketoconazole, and others), estrogens, Luteinizing Hormone Releasing Hormone (LHRH) agonist/antagonists. Prior therapy with 5α-reductase inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1.

    2. Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.

    3. Prior systemic treatment with an azole drug within two weeks of start of treatment.

    4. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.

    5. Clinically significant cardiovascular disease within 6 months of study treatment including:

    • Severe or unstable angina;

    • Myocardial infarction;

    • Symptomatic congestive heart failure;

    • New York Heart Association (NYHA) class II-IV heart disease;

    • Arterial or venous thromboembolic events (such as pulmonary embolism cerebrovascular accident including transient ischemic attacks);

    • History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);

    • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 470 msec;

    • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;

    • Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.

    1. History of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).

    2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs.

    3. Severe hepatic impairment (Child-Pugh Class C).

    4. Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated.

    5. History of pituitary or adrenal dysfunction.

    6. Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.

    7. Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular, or inhaled corticosteroids are permitted.

    8. Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide.

    9. Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.

    10. Major surgery or radiation therapy within 30 days of screening visit. Participants who have had a major surgery within 30 days of screening visit may be eligible provided the treating investigator deems that the participant is at low risk for complications.

    11. Any condition that in the opinion of the investigator would preclude participation in this study.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of California, San Diego Moores Cancer CenterLa JollaCaliforniaUnited States92093
    2Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02115
    3Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
    4Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Janssen Scientific Affairs, LLC

    Investigators

    • Principal Investigator: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Mary-Ellen Taplin, MD, Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02903368
    Other Study ID Numbers:
    • 16-223
    First Posted:
    Sep 16, 2016
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Mary-Ellen Taplin, MD, Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThis is a 2-part study: In part 1, patients will be randomized in 1:1 ratio to receive 6 months of AAPL (Arm 1A) versus 6 months of APL (Arm 1B) followed by RP, stratified by risk factor. In part 2 (post-RP), patients will be randomized in 1:1 ratio to receive an additional 12 months of AAPL (Arm 2A) or observation (Arm 2B) stratified by type of neoadjuvant therapy and pathological T-stage after RP but before cycle 7 day 1 following neoadjuvant therapy.
    Pre-assignment DetailThe part 2 of the study is still in progression and the final data has not been collected
    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 months consistentEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Period Title: Overall Study
    STARTED5959
    COMPLETED5559
    NOT COMPLETED40

    Baseline Characteristics

    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)Total
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 monthsTotal of all reporting groups
    Overall Participants5959118
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    62
    58
    61
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    59
    100%
    59
    100%
    118
    100%
    Race/Ethnicity, Customized (participants) [Number]
    White
    55
    93.2%
    48
    81.4%
    103
    87.3%
    Black or African American
    3
    5.1%
    6
    10.2%
    9
    7.6%
    Asian
    0
    0%
    2
    3.4%
    2
    1.7%
    Other
    1
    1.7%
    3
    5.1%
    4
    3.4%
    Region of Enrollment (participants) [Number]
    United States
    59
    100%
    59
    100%
    118
    100%

    Outcome Measures

    1. Primary Outcome
    TitleCombined pCR or MRD Rate [Part 1]
    DescriptionPathological 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 Frameat 6 month

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: AAPLArm B: APL
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Count of Participants [Participants]
    12
    20.3%
    12
    20.3%
    2. Primary Outcome
    TitleMedian Biochemical Progression Free Survival (bPFS) [Part 2]
    DescriptionbPFS will be defined as the time from the date of randomization to the date of first evidence of disease progression (defined per protocol) or death from all causes, censored at the date of last disease follow-up.
    Time FrameAt 3 years post-RP

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleRate of pCR at RP
    DescriptionPathological Complete Response (pCR) is defined as the absence of morphologically identifiable carcinoma in the RP specimen at radical prostatectomy (RP).
    Time Frameat 6 month

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: AAPLArm B: APL
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Number (95% Confidence Interval) [percentage of participants]
    0.13
    0.2%
    0.10
    0.2%
    4. Secondary Outcome
    TitleMedian of Residual Cancer Burden (RCB) at RP
    DescriptionRCB 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 FrameAt 6 month

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: AAPLArm B: APL
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Median (Full Range) [cm^3]
    0.023
    0.075
    5. Secondary Outcome
    TitlePercentage of Participants With Presenting Cribriform at RP
    DescriptionPatients were 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 (Radical Prostatectomy). Cribriform at RP was evaluated by central pathology review at the completion of the study.
    Time FrameAt RP (6 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Number (95% Confidence Interval) [percentage of participants]
    1.8
    3.1%
    0
    0%
    6. Secondary Outcome
    TitleFrequency of Presenting Intraductal Carcinoma at RP
    DescriptionPatients were 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 (Radical Prostatectomy). Intraductal carcinoma at RP was evaluated by central pathology review at the completion of the study.
    Time FrameAt RP (6 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm B: APL Adjuvant Therapy (Part 1)
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Number (95% Confidence Interval) [percentage of participants]
    27.3
    46.3%
    32.2
    54.6%
    7. Secondary Outcome
    TitleFrequency of Positive Surgical Margins
    DescriptionPathologic specimens will be assessed and counted for positive surgical margins at the time of RP.
    Time FrameAt RP (6 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    Measure Participants5559
    Number (95% Confidence Interval) [percentage of participants]
    7.3
    12.4%
    11.9
    20.2%
    8. Secondary Outcome
    TitleMedian Pre-RP PSA Nadir
    Descriptionprostate specific antigen (PSA) nadir defined as nadir PSA < 0.2 ng/mL
    Time FrameAt 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    TitleIntra-operative and Post-operative Complications Following RP Between Treatment Arms (1A and 1B)
    Description
    Time FrameAt 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameAdverse events during neoadjuvant therapy should be collected from the date of informed consent is signed until 30 days after discontinuation of the neoadjuvant therapy. SAEs will be reported starting from the first dose of the study drugs. AE data is collected at pre-study, Day 1 of each cycle (+/-2 days), until removal from the neoadjuvant therapy.
    Adverse Event Reporting Description Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
    Arm/Group TitleArm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Arm/Group DescriptionEligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 monthsEligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months
    All Cause Mortality
    Arm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/55 (0%) 0/59 (0%)
    Serious Adverse Events
    Arm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/55 (10.9%) 4/59 (6.8%)
    Investigations
    Alanine aminotransferase increased1/55 (1.8%) 2/59 (3.4%)
    Aspartate aminotransferase increased1/55 (1.8%) 1/59 (1.7%)
    Vascular disorders
    Hypertension5/55 (9.1%) 1/59 (1.7%)
    Other (Not Including Serious) Adverse Events
    Arm 1A: AAPL Neoadjuvant Therapy (Part 1)Arm 1B: APL Adjuvant Therapy (Part 1)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total55/55 (100%) 59/59 (100%)
    Blood and lymphatic system disorders
    Anemia4/55 (7.3%) 8/59 (13.6%)
    Febrile neutropenia0/55 (0%) 1/59 (1.7%)
    Leukocytosis1/55 (1.8%) 0/59 (0%)
    Blood and lymphatic system disorders - Other0/55 (0%) 1/59 (1.7%)
    Cardiac disorders
    Palpitations0/55 (0%) 3/59 (5.1%)
    Sinus tachycardia0/55 (0%) 1/59 (1.7%)
    Ear and labyrinth disorders
    Tinnitus0/55 (0%) 1/59 (1.7%)
    Vertigo0/55 (0%) 1/59 (1.7%)
    Endocrine disorders
    Hyperthyroidism0/55 (0%) 1/59 (1.7%)
    Hypothyroidism2/55 (3.6%) 0/59 (0%)
    Eye disorders
    Dry eye0/55 (0%) 1/59 (1.7%)
    Flashing lights1/55 (1.8%) 0/59 (0%)
    Photophobia1/55 (1.8%) 0/59 (0%)
    Gastrointestinal disorders
    Abdominal pain3/55 (5.5%) 1/59 (1.7%)
    Bloating1/55 (1.8%) 1/59 (1.7%)
    Constipation5/55 (9.1%) 3/59 (5.1%)
    Diarrhea3/55 (5.5%) 3/59 (5.1%)
    Dyspepsia0/55 (0%) 1/59 (1.7%)
    Gastroesophageal reflux disease2/55 (3.6%) 1/59 (1.7%)
    Hemorrhoids1/55 (1.8%) 0/59 (0%)
    Mucositis oral1/55 (1.8%) 0/59 (0%)
    Nausea3/55 (5.5%) 6/59 (10.2%)
    Rectal hemorrhage0/55 (0%) 2/59 (3.4%)
    Small intestinal mucositis1/55 (1.8%) 0/59 (0%)
    Small intestinal perforation0/55 (0%) 1/59 (1.7%)
    Vomiting1/55 (1.8%) 3/59 (5.1%)
    Gastrointestinal disorders - Other1/55 (1.8%) 4/59 (6.8%)
    General disorders
    Chills0/55 (0%) 1/59 (1.7%)
    Edema limbs2/55 (3.6%) 1/59 (1.7%)
    Facial pain1/55 (1.8%) 0/59 (0%)
    Fatigue30/55 (54.5%) 30/59 (50.8%)
    Fever0/55 (0%) 2/59 (3.4%)
    Flu like symptoms1/55 (1.8%) 1/59 (1.7%)
    Injection site reaction2/55 (3.6%) 1/59 (1.7%)
    Irritability1/55 (1.8%) 1/59 (1.7%)
    Localized edema0/55 (0%) 2/59 (3.4%)
    Non-cardiac chest pain0/55 (0%) 1/59 (1.7%)
    Pain4/55 (7.3%) 2/59 (3.4%)
    Hepatobiliary disorders
    Hepatobiliary disorders - Other2/55 (3.6%) 2/59 (3.4%)
    Infections and infestations
    Mucosal infection1/55 (1.8%) 0/59 (0%)
    Papulopustular rash1/55 (1.8%) 1/59 (1.7%)
    Pharyngitis1/55 (1.8%) 0/59 (0%)
    Pleural infection1/55 (1.8%) 0/59 (0%)
    Rash pustular2/55 (3.6%) 0/59 (0%)
    Sinusitis1/55 (1.8%) 0/59 (0%)
    Tooth infection1/55 (1.8%) 0/59 (0%)
    Upper respiratory infection1/55 (1.8%) 0/59 (0%)
    Urinary tract infection0/55 (0%) 2/59 (3.4%)
    Infections and infestations - Other1/55 (1.8%) 1/59 (1.7%)
    Injury, poisoning and procedural complications
    Hip fracture1/55 (1.8%) 0/59 (0%)
    Urethral anastomotic leak0/55 (0%) 1/59 (1.7%)
    Vascular access complication0/55 (0%) 1/59 (1.7%)
    Injury, poisoning and procedural complications - Other1/55 (1.8%) 0/59 (0%)
    Investigations
    Alanine aminotransferase increased14/55 (25.5%) 22/59 (37.3%)
    Alkaline phosphatase increased0/55 (0%) 2/59 (3.4%)
    Aspartate aminotransferase increased13/55 (23.6%) 20/59 (33.9%)
    Blood bilirubin increased0/55 (0%) 5/59 (8.5%)
    Cholesterol high4/55 (7.3%) 3/59 (5.1%)
    Lymphocyte count decreased0/55 (0%) 1/59 (1.7%)
    Neutrophil count decreased1/55 (1.8%) 0/59 (0%)
    Weight gain1/55 (1.8%) 3/59 (5.1%)
    Weight loss0/55 (0%) 2/59 (3.4%)
    Investigations - Other1/55 (1.8%) 1/59 (1.7%)
    Metabolism and nutrition disorders
    Anorexia2/55 (3.6%) 0/59 (0%)
    Hyperglycemia2/55 (3.6%) 3/59 (5.1%)
    Hyperkalemia0/55 (0%) 1/59 (1.7%)
    Hypertriglyceridemia3/55 (5.5%) 1/59 (1.7%)
    Hyperuricemia0/55 (0%) 1/59 (1.7%)
    Hypokalemia2/55 (3.6%) 4/59 (6.8%)
    Hypomagnesemia1/55 (1.8%) 0/59 (0%)
    Hyponatremia0/55 (0%) 1/59 (1.7%)
    Metabolism and nutrition disorders - Other0/55 (0%) 1/59 (1.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia1/55 (1.8%) 3/59 (5.1%)
    Back pain3/55 (5.5%) 2/59 (3.4%)
    Bone pain1/55 (1.8%) 0/59 (0%)
    Generalized muscle weakness0/55 (0%) 5/59 (8.5%)
    Joint effusion0/55 (0%) 1/59 (1.7%)
    Myalgia2/55 (3.6%) 3/59 (5.1%)
    Pain in extremity2/55 (3.6%) 2/59 (3.4%)
    Musculoskeletal and connective tissue disorder - Other5/55 (9.1%) 8/59 (13.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other0/55 (0%) 1/59 (1.7%)
    Nervous system disorders
    Akathisia1/55 (1.8%) 0/59 (0%)
    Cognitive disturbance2/55 (3.6%) 1/59 (1.7%)
    Dizziness3/55 (5.5%) 4/59 (6.8%)
    Dysgeusia5/55 (9.1%) 1/59 (1.7%)
    Dysphasia1/55 (1.8%) 0/59 (0%)
    Headache8/55 (14.5%) 11/59 (18.6%)
    Memory impairment1/55 (1.8%) 2/59 (3.4%)
    Syncope1/55 (1.8%) 2/59 (3.4%)
    Nervous system disorders - Other1/55 (1.8%) 1/59 (1.7%)
    Restlessness2/55 (3.6%) 1/59 (1.7%)
    Psychiatric disorders - Other1/55 (1.8%) 5/59 (8.5%)
    Psychiatric disorders
    Agitation2/55 (3.6%) 2/59 (3.4%)
    Anxiety2/55 (3.6%) 0/59 (0%)
    Depression2/55 (3.6%) 4/59 (6.8%)
    Insomnia10/55 (18.2%) 6/59 (10.2%)
    Libido decreased3/55 (5.5%) 7/59 (11.9%)
    Personality change0/55 (0%) 1/59 (1.7%)
    Renal and urinary disorders
    Hematuria1/55 (1.8%) 3/59 (5.1%)
    Urinary frequency7/55 (12.7%) 6/59 (10.2%)
    Urinary incontinence22/55 (40%) 21/59 (35.6%)
    Urinary retention2/55 (3.6%) 1/59 (1.7%)
    Urinary tract pain0/55 (0%) 3/59 (5.1%)
    Urinary urgency1/55 (1.8%) 1/59 (1.7%)
    Renal and urinary disorders - Other, specify3/55 (5.5%) 1/59 (1.7%)
    Reproductive system and breast disorders
    Erectile dysfunction10/55 (18.2%) 13/59 (22%)
    Genital edema1/55 (1.8%) 0/59 (0%)
    Gynecomastia1/55 (1.8%) 0/59 (0%)
    Pelvic pain0/55 (0%) 1/59 (1.7%)
    Penile pain0/55 (0%) 1/59 (1.7%)
    Scrotal pain0/55 (0%) 1/59 (1.7%)
    Testicular disorder0/55 (0%) 1/59 (1.7%)
    Testicular pain1/55 (1.8%) 1/59 (1.7%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis1/55 (1.8%) 0/59 (0%)
    Cough2/55 (3.6%) 5/59 (8.5%)
    Dyspnea3/55 (5.5%) 2/59 (3.4%)
    Nasal congestion1/55 (1.8%) 1/59 (1.7%)
    Voice alteration1/55 (1.8%) 0/59 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia1/55 (1.8%) 0/59 (0%)
    Dry skin3/55 (5.5%) 1/59 (1.7%)
    Rash acneiform1/55 (1.8%) 0/59 (0%)
    Rash maculo-papular12/55 (21.8%) 3/59 (5.1%)
    Skin and subcutaneous tissue disorders - Other2/55 (3.6%) 0/59 (0%)
    Vascular disorders
    Flushing1/55 (1.8%) 0/59 (0%)
    Hot flashes51/55 (92.7%) 50/59 (84.7%)
    Hypertension16/55 (29.1%) 11/59 (18.6%)
    Hypotension0/55 (0%) 1/59 (1.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleMary-Ellen Taplin, MD
    OrganizationDana-Farber Cancer Institute
    Phone617-582-7221
    Emailmtaplin@partners.org
    Responsible Party:
    Mary-Ellen Taplin, MD, Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02903368
    Other Study ID Numbers:
    • 16-223
    First Posted:
    Sep 16, 2016
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Sep 1, 2021