Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

NCT02903368 | Completed Phase 2 Results DMC

• 1 other identifier: 16-223
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 4

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).

Conditions

Prostate Cancer

Keywords

abiraterone acetate; apalutamide; leuprolide; prednisone; neoadjuvant therapy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At 3 years post RP

Secondary Outcomes (15)

• Rate of pCR at RP (Part 1)

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

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

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

• Frequency of Presenting Cribriform at RP (Part 1)

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

• Frequency of Presenting Intraductal Carcinoma at RP (Part 1)

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

• Frequency of Positive Surgical Margins at RP (Part 1)

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

Study Arms (4)

Arm 1A: AAPL Neoadjuvant Therapy [Part 1]

EXPERIMENTAL

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; Drug: Leuprolide; Drug: Prednisone; Drug: Abiraterone Acetate

Arm 1B: APL Neoadjuvant Therapy [Part 1]

EXPERIMENTAL

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; Drug: Prednisone; Drug: Abiraterone Acetate

Arm 2A: AAPL Adjuvant Therapy [Part 2]

EXPERIMENTAL

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; Drug: Leuprolide; Drug: Prednisone; Drug: Abiraterone Acetate

Arm 2B: Observation [Part 2]

NO INTERVENTION

Interventions

Apalutamide DRUG

Also known as: JNJ-56021927, ARN-509

Arm 1A: AAPL Neoadjuvant Therapy [Part 1]; Arm 2A: AAPL Adjuvant Therapy [Part 2]

Leuprolide DRUG

Also known as: Lupron, Eligard

Arm 1A: AAPL Neoadjuvant Therapy [Part 1]; Arm 1B: APL Neoadjuvant Therapy [Part 1]; Arm 2A: AAPL Adjuvant Therapy [Part 2]

Prednisone DRUG

Also known as: Deltasone

Arm 1A: AAPL Neoadjuvant Therapy [Part 1]; Arm 1B: APL Neoadjuvant Therapy [Part 1]; Arm 2A: AAPL Adjuvant Therapy [Part 2]

Abiraterone Acetate DRUG

Also known as: Zytiga

Arm 1A: AAPL Neoadjuvant Therapy [Part 1]; Arm 1B: APL Neoadjuvant Therapy [Part 1]; Arm 2A: AAPL Adjuvant Therapy [Part 2]

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male ≥ 18 years of age.
• 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).
• 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.
• 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).
• 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.
• Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• 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)

You may not qualify if:

• 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.
• Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
• Prior systemic treatment with an azole drug within two weeks of start of treatment.
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone \< 200 ng/dL.
• 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.
• 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).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (4)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (2)

• McKay RR, Xie W, Yang X, Acosta A, Rathkopf D, Laudone VP, Bubley GJ, Einstein DJ, Chang P, Wagner AA, Kane CJ, Preston MA, Kilbridge K, Chang SL, Choudhury AD, Pomerantz MM, Trinh QD, Kibel AS, Taplin ME. 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. Cancer. 2024 May 1;130(9):1629-1641. doi: 10.1002/cncr.35170. Epub 2024 Jan 1.

  PMID: 38161319 DERIVED

• McKay RR, Xie W, Ye H, Fennessy FM, Zhang Z, Lis R, Calagua C, Rathkopf D, Laudone VP, Bubley GJ, Einstein DJ, Chang PK, Wagner AA, Parsons JK, Preston MA, Kilbridge K, Chang SL, Choudhury AD, Pomerantz MM, Trinh QD, Kibel AS, Taplin ME. Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer. J Urol. 2021 Jul;206(1):80-87. doi: 10.1097/JU.0000000000001702. Epub 2021 Mar 8.

  PMID: 33683939 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Leuprolide; luprolide acetate gel depot; Prednisone; Abiraterone Acetate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstenes; Androstanes

Results Point of Contact

• Title: Mary-Ellen Taplin, MD
• Organization: Dana-Farber Cancer Institute

mtaplin@partners.org

617-582-7221

Study Officials

• Mary-Ellen Taplin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mary-Ellen Taplin, MD

Study Record Dates

• First Submitted: August 24, 2016
• First Posted: September 16, 2016
• Study Start: October 19, 2016
• Primary Completion: April 5, 2022
• Study Completion: July 10, 2024
• Last Updated: June 13, 2025
• Results First Posted: September 5, 2021

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)