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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

Overview

Status
Completed
Phase
Phase 2
Enrollment
118 participants (actual)
Sponsor
Dana-Farber Cancer Institute · Other
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
19 Oct 2016
Primary completion
5 Apr 2022
Completion
10 Jul 2024
First posted
16 Sept 2016 (estimated)
Last update posted
13 Jun 2025
Conditions
Prostate Cancer

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20162018202020222024
  1. Ph 2

    Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

    NCT02903368

    19 Oct 2016 to 10 Jul 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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).

Interventions

  • ApalutamideDrug
  • LeuprolideDrug
  • PrednisoneDrug
  • Abiraterone AcetateDrug

Arms4

  • 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

  • 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

  • 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

  • No intervention

    Arm 2B: Observation [Part 2]

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Combined pCR or MRD Rate [Part 1]

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    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. Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2]

    Time frame · At 3 years post RP

    Registry description

    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.

Secondary outcomes(15)
  1. Rate of pCR at RP (Part 1)

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    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 (Part 1)

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    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).

  3. Frequency of Presenting Cribriform at RP (Part 1)

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    Presence or cribriform was evaluated by central pathology review of specimens at radical prostatectomy (RP).

  4. Frequency of Presenting Intraductal Carcinoma at RP (Part 1)

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    Intraductal carcinoma was evaluated by central pathology review of specimens at Radical Prostatectomy (RP).

  5. Frequency of Positive Surgical Margins at RP (Part 1)

    Time frame · Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    Pathologic specimens were centrally reviewed and counted for positive surgical margins at the time of Radical Prostatectomy (RP).

  6. Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1)

    Time frame · Assessed on day 1 of each cycle (1 cycle=28 +/- 2 days), up to 6 months from the initiation of neoadjuvant therapy.

    Registry description

    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.

  7. Frequency of Presenting Intra-operative Complications Following RP (Part 1)

    Time frame · Assessed post-RP, at 6 months from the initiation of neoadjuvant therapy.

    Registry description

    Intra-operative complications were collected via questionnaire following Radical Prostatectomy.

  8. Biochemical Progression Free Survival (bPFS) Rate at 2 Years Post RP [Part 2]

    Time frame · At 2 years post RP

    Registry description

    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.

  9. Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2]

    Time frame · At 4 years post RP

    Registry description

    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.

  10. Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2)

    Time frame · At 2-years post RP

    Registry description

    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.

  11. Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2)

    Time frame · At 3 years post RP

    Registry description

    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.

  12. Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2)

    Time frame · At 4-years post RP

    Registry description

    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.

  13. Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2)

    Time frame · At 6-months post-RP

    Registry description

    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.

  14. Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2)

    Time frame · At 12-months post-RP

    Registry description

    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.

  15. Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2)

    Time frame · At 24-months post-RP

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Combined pCR or MRD Rate [Part 1]

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)12
Arm 1B: APL Neoadjuvant Therapy (Part 1)12
Primary outcomeNumber· At 3 years post RP

Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2]

GroupValue (percentage of subjects)
Arm 2A: AAPL Adjuvant Therapy (Part 2)81
Arm 2B: Observation (Part 2)72
Secondary and other outcome results(6)
Secondary outcomeCount of participants· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Rate of pCR at RP (Part 1)

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)7
Arm 1B: APL Neoadjuvant Therapy (Part 1)6
Secondary outcomeMedian· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Median of Residual Cancer Burden (RCB) at RP (Part 1)

GroupValue ((cm^3) * %)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)0.023
Arm 1B: APL Neoadjuvant Therapy (Part 1)0.075
Secondary outcomeCount of participants· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Frequency of Presenting Cribriform at RP (Part 1)

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)1
Arm 1B: APL Neoadjuvant Therapy (Part 1)0
Secondary outcomeCount of participants· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Frequency of Presenting Intraductal Carcinoma at RP (Part 1)

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)15
Arm 1B: APL Neoadjuvant Therapy (Part 1)19
Secondary outcomeCount of participants· Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.

Frequency of Positive Surgical Margins at RP (Part 1)

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)4
Arm 1B: APL Neoadjuvant Therapy (Part 1)7
Secondary outcomeCount of participants· Assessed on day 1 of each cycle (1 cycle=28 +/- 2 days), up to 6 months from the initiation of neoadjuvant therapy.

Percent of Participants With Nadir PSA < 0.2 ng/mL Prior to RP (Part 1)

GroupValue (Participants)
Arm 1A: AAPL Neoadjuvant Therapy (Part 1)55
Arm 1B: APL Neoadjuvant Therapy (Part 1)58

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
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 months0 / 598 / 5959 / 59
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 months0 / 595 / 5959 / 59
Arm 2A: AAPL Adjuvant Therapy (Part 2)Eligible participants will be randomized to receive adjuvant AAPL post surgery: 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 Of the 42 patients randomized to Arm 2A, only 37 patients received the AAPL treatment; 5 patients declined protocol treatment after part-2 randomization. Therefore, toxicities for Arm 2A were reported among the 37 patients who actually received AAPL treatment.0 / 374 / 3730 / 37
Arm 2B: Observation (Part 2)Eligible participants will be randomized to the observation arm post surgery. Of the 40 patients randomized to Arm 2B (observation), 38 remained on observation and 2 received non-protocol therapy. Therefore, the AE analysis for Arm 2B included the 38 patients on observation, excluding 2 patient receiving non-protocol therapy.0 / 380 / 3828 / 38

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

More studies

2 studies on this page

Indexing hint: Randomized controlled trial · 2024

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

McKay et al. 2024Cancercited by 13

PMID 38161319DOI 10.1002/cncr.35170PUB-38161319

Full text at the publisher
Publisher page

Indexing hint: Randomized controlled trial · 2021

Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

McKay et al. 2021The Journal of urologycited by 73

PMID 33683939PMC9807004DOI 10.1097/ju.0000000000001702PUB-33683939

Rights unknown
Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedLin HM, Yang X, Centenera MM, Huynh K, Giles C, Dehairs J, Swinnen JV, Hoy AJ, Meikle PJ, Butler LM, Taplin ME, Horvath LG. Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer. JCO Precis Oncol. 2024 Jul;8:e2400260. doi: 10.1200/PO.24.00260. PMID 39074346

Eligibility

Who could join, as posted.

Sex
Male
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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). 5. 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. 6. Participants must be candidates for RP and considered surgically resectable by urologic evaluation. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 8. 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 9. 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. 10. 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. 6. 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). 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs. 8. Severe hepatic impairment (Child-Pugh Class C). 9. Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated. 10. History of pituitary or adrenal dysfunction. 11. Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug. 12. 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. 13. Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide. 14. 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. 15. 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. 16. Any condition that in the opinion of the investigator would preclude participation in this study.

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