Prostate CancerPhase 2NCT02903368
Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy
A Phase 2 study testing Apalutamide, Leuprolide and Prednisone in people with Prostate Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Apalutamide, Leuprolide and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 4 sitesUnited States
- Study dates
- 19 Oct 2016to 10 Jul 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 21Show fewer
- 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)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Serum albumin ≥ 3.0 g/dL
- Serum creatinine < 2.0 x ULN
- PTT≤60
- 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.
- 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.
Who cannot join
- 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;
Show all 25Show fewer
- 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).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs.
- Severe hepatic impairment (Child-Pugh Class C).
- Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated.
- History of pituitary or adrenal dysfunction.
- Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
- 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.
- Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide.
- 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.
- 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.
- Any condition that in the opinion of the investigator would preclude participation in this study.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
University of California, San Diego Moores Cancer Center
La Jolla, California, 92093
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Randomized Study Of Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide For Intermediate-High Risk Prostate Cancer Undergoing Prostatectomy
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).
Read the 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).
- Conditions
- Prostate Cancer
- Being tested
- Apalutamide, Leuprolide, Prednisone, Abiraterone Acetate
- Keywords
- abiraterone acetate, apalutamide, leuprolide, prednisone, neoadjuvant therapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApalutamideDrug
Also called JNJ-56021927, ARN-509
LeuprolideDrug
Also called Lupron, Eligard
PrednisoneDrug
Also called Deltasone
Abiraterone AcetateDrug
Also called Zytiga
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Apalutamide; Drug: Leuprolide; Drug: Prednisone; Drug: Abiraterone Acetate |
| Arm 2B: Observation [Part 2] | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At 3 years post RP
Secondary outcomes (15)
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).
Measured: 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).
Measured: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Cribriform at RP (Part 1)
Presence or cribriform was evaluated by central pathology review of specimens at radical prostatectomy (RP).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At 24-months post-RP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study start19 Oct 2016
- Primary completion5 Apr 2022
- Study completion10 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Responsible party
- Principal investigator, Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
- Investigators
- Mary-Ellen Taplin, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02903368
- Sponsor's protocol ID
- 16-223
- Status last verified
- Jun 2025
- First submitted
- 24 Aug 2016
- Last updated
- 13 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lin 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.
PubMed 39074346McKay 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.
PubMed 38161319McKay 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.
PubMed 33683939
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study Of Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide For Intermediate-High Risk Prostate Cancer Undergoing Prostatectomy
- ClinicalTrials.gov ID
- NCT02903368
- Acronym / sponsor ID
- 16-223
- Conditions
- Prostate Cancer
- Keywords
- abiraterone acetate, apalutamide, leuprolide, prednisone, neoadjuvant therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Study start
- 19 Oct 2016 (actual)
- Primary completion
- 5 Apr 2022 (actual)
- Study completion
- 10 Jul 2024 (actual)
- First posted
- 16 Sep 2016 (estimated)
- Results
- Posted 5 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1A: AAPL Neoadjuvant Therapy [Part 1] | Experimental | Drug: Apalutamide, Drug: Leuprolide, Drug: Prednisone, Drug: Abiraterone AcetateEligible 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 |
| Arm 1B: APL Neoadjuvant Therapy [Part 1] | Experimental | Drug: Leuprolide, Drug: Prednisone, Drug: Abiraterone AcetateEligible 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 |
| Arm 2A: AAPL Adjuvant Therapy [Part 2] | Experimental | Drug: Apalutamide, Drug: Leuprolide, Drug: Prednisone, Drug: Abiraterone AcetateEligible 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 |
| Arm 2B: Observation [Part 2] | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
- 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.
Key exclusion criteria (25 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApalutamideAlso: JNJ-56021927, ARN-509 | Drug | Arm 1A: AAPL Neoadjuvant Therapy [Part 1], Arm 2A: AAPL Adjuvant Therapy [Part 2] |
| LeuprolideAlso: Lupron, Eligard | Drug | Arm 1A: AAPL Neoadjuvant Therapy [Part 1], Arm 1B: APL Neoadjuvant Therapy [Part 1], Arm 2A: AAPL Adjuvant Therapy [Part 2] |
| PrednisoneAlso: Deltasone | Drug | Arm 1A: AAPL Neoadjuvant Therapy [Part 1], Arm 1B: APL Neoadjuvant Therapy [Part 1], Arm 2A: AAPL Adjuvant Therapy [Part 2] |
| Abiraterone AcetateAlso: Zytiga | Drug | Arm 1A: AAPL Neoadjuvant Therapy [Part 1], Arm 1B: APL Neoadjuvant Therapy [Part 1], Arm 2A: AAPL Adjuvant Therapy [Part 2] |
Primary outcome
Combined pCR or MRD Rate [Part 1]
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
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.
Biochemical Progression Free Survival (bPFS) Rate at 3 Years Post RP [Part 2]
Time frame: At 3 years post RP
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.
15 secondary outcomes
Rate of pCR at RP (Part 1)
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)
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Cribriform at RP (Part 1)
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Presenting Intraductal Carcinoma at RP (Part 1)
Time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.
Frequency of Positive Surgical Margins at RP (Part 1)
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)
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)
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]
Time frame: At 2 years post RP
Biochemical Progression Free Survival (bPFS) Rate at 4 Years Post RP [Part 2]
Time frame: At 4 years post RP
Rate of Freedom From Further Anti-cancer Therapy at 2-years Post RP (Part 2)
Time frame: At 2-years post RP
Rate of Freedom From Further Anti-cancer Therapy at 3-years Post RP (Part 2)
Time frame: At 3 years post RP
Rate of Freedom From Further Anti-cancer Therapy at 4-years Post RP (Part 2)
Time frame: At 4-years post RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 6-months Post-RP (Part 2)
Time frame: At 6-months post-RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 12-months Post-RP (Part 2)
Time frame: At 12-months post-RP
Mean Scores for Quality of Life (QOL) Questionnaires EPIC-26 at 24-months Post-RP (Part 2)
Time frame: At 24-months post-RP
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39074346Lin 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.
- Derived from this study: PubMed 38161319McKay 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.
- Derived from this study: PubMed 33683939McKay 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.
- Individual participant dataSharing planned: No
Related trials for Prostate Cancer
RecruitingObservational study
Imaging Studies to Check the Local Response of Prostate Cancer to Radiation Therapy
Prostatic Neoplasms, Prostate Cancer
Active, not recruitingPhase 2
Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer
Prostate Cancer
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary-Ellen Taplin, MD principal investigator
Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apalutamide, Leuprolide and Prednisone in people with Prostate Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined pCR or MRD Rate [Part 1] (time frame: Assessed from RP specimens, at 6 months from the initiation of neoadjuvant therapy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02903368, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2025.