AzTrials
AzTrials

Prostate CancerPhase 2NCT03436654

Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma

A Phase 2 study testing Apalutamide, Abiraterone Acetate and Prednisone in people with Prostate Cancer, run by Memorial Sloan Kettering Cancer Center at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to test if treatment with medications that reduce the male hormone level in the participant's body for a few months before surgery can shrink prostate cancer as much as possible, which might reduce the chances of the cancer coming back in the future. 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, Abiraterone Acetate and Prednisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
11 sitesUnited States
Study dates
21 Jun 2018to 14 Feb 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization) NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
  • Male aged 18 years and above
  • Serum testosterone of ≥150 ng/dL (For Cohorts A and B1, testosterone level requirement is exempted if they are already on ADT prior to treatment start. For Cohort B2, subjects will be considered eligible if their testosterone is currently ≥150 ng/dl).
  • Histologically confirmed adenocarcinoma of the prostate, who meet the following criteria:
  • Cohort A
  • Clinically localized disease with histologically confirmed adenocarcinoma of the prostate with either ≥3 positive cores or 2 positive cores if \>1cm in length with at least 50% tumor content WITH
Show all 46Show fewer
  • With Gleason score 8-10 OR
  • Gleason 4+3 with one of the following features:
  • PSA ≥ 20 mg/mL within 2 months prior to diagnostic biopsy
  • MRI suspicious for radiographic ≥T3 disease (if urologist deems tumor is resectable at baseline); defined as \>75% probability of extracapsular extension or seminal vesicle invasion in the opinion of the reading radiologist.
  • OR
  • Gleason 3+4 or 4+3 and Oncotype DX Genomic Prostate Score of \>40
  • With or without clinical N1 (size \>1.5cm in the short axis) (Gleason score requirement can be omitted if node positive)
  • OR
  • Cohort B1
  • Newly diagnosed low-volume metastatic disease with either.
  • Bone metastases as documented by CT, MRI or radionuclide bone scan amenable to treatment with a maximum of 3 radiation isocenters* These lesions must have a structural correlate on CT or MRI to allow for adequate radiation targeting
  • (note:subjects with PET scans that show osseous metastases that would not be amenable to 3-isocenter radiation treatment are still eligible if conventional imaging shows osseous disease that can be treated with 3 radiation isocenters) And/or
  • Retroperitoneal nodes up to the level of the renal hilum with/without pelvic nodal metastasis \>1.5cm in the short axis
  • NOTE: For Cohort B1, biopsy confirmation of metastases is strongly encouraged if safe and feasible, but not required
  • OR
  • Cohort B2 (Cohort B2 expansion)
  • Biochemically persistent/recurrent disease (defined as PSA \>0.2) after RP ± extended pelvic nodal dissection with metastatic lesions identified on PSMAb PET scans
  • PSMA PET evidence of M1a/M1b disease that could be covered in up to 3 radiation plans (note that the isocenter for planned prostate bed/pelvic nodal irradiation does not count towards the 3 isocenter limit)
  • No radiographic evidence of local or regional recurrence on imaging in subjects with prior salvage radiation to these areas.
  • Prior salvage radiotherapy is permitted. Prior metastasis-directed radiation is not permitted.
  • Castration sensitive disease
  • Multiple lesions within one isocenter may be permitted upon review by the sponsor's radiation oncologist
  • ECOG performance status of ≤ 1
  • NOTE: For Cohort B2, biopsy confirmation of metastases is strongly encouraged if safe and feasible, but not required
  • Adequate bone marrow, hepatic and renal function, as evidenced within 28 days prior to treatment start by:
  • ANC ≥ 1500/µl
  • Hemoglobin ≥ 9g/dL
  • Platelet count ≥ 100,000/µl
  • Serum Creatinine GFR ≥30 mL/min
  • Porassium within institutional normal range
  • Total Bilirubin ≤ 1.5 x ULN (Note: In subjects with Gilbert\'s syndrome, if total bilirubin is \>1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible)
  • Albumin ≥ 3.0 g/dL
  • SGOT (AST) ≤ 2.5 x ULN
  • SGPT (ALT) ≤ 2.5 x ULN
  • Subjects must have a clinical T stage documented by the treating urologist/medical oncologist within 90 days prior to treatment start using the 7th edition AJCC staging system, recorded as the urologist\'s/medical oncologist\'s best clinical assessment of extent of local disease by digital rectal examination and/or available imaging studies such as transrectral ultrasound, CT scan, and/or MRI. Applicable to Cohorts A and B1 only.
  • The primary tumor must be considered unresectable by RP based on initial imaging with gross negative margins as determined by a urologist and documented as such. (Applicable to Cohorts A and B1 only)
  • Recovery of reversible effects of prior surgery (i.e., incisional pain, wound drainage) to Grade ≤1, and at least 4 weeks from prior surgery to treatment start. (biopsy excluded)
  • Able to swallow the study drug(s) whole as a tablet
  • Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least one hour before and for at least two hours after the dose of abiraterone acetate is taken (Not applicable to Cohort B2 expansion) (Note: apalutamide does not have to be taken on an empty stomach.)
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees 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. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.

Who cannot join

  • Prior treatment for prostate cancer including prior surgery (excluding TURP and subjects with rising PSA after RP), pelvic lymph node dissection, and/or radiation therapy unless the subject is eligible for Cohort B2. (Applicable to cohorts A and B1 only).
  • Prior cytotoxic chemotherapy or biologic therapy for prostate cancer
  • Up to 2 months of prior ADT with GnRH antagonist/agonist at time of treatment start. Bicalutamide given for ≤ 12 months at the time of registration as flare prevention is allowed. For Cohort B2, prior ADT and/or first generation anti-androgen treatment in the (neo)adjuvant and/or salvage setting in conjunction with radiation or surgery is allowed provided last effective dose of ADT and/or first generation anti-androgen is \> 12 months prior to the on treatment date and total duration of prior therapy is 12 months or lesser, and their testosterone is currently \>150ng/dL.
  • Prior exposure to ketoconazole (systemic), abiraterone acetate, enzalutamide or other agents targeting the AR signaling pathway
  • Concomitant therapy with any other experimental drug
  • Known brain, liver, lung or other visceral metastasis (except for retroperitoneal and/or pelvic nodal metastases as per inclusion criteria)
Show all 33Show fewer
  • Prior prostate cancer metastasis-directed therapies
  • Currently active second malignancy or past history of malignancies diagnosed within the last 2 years that require active therapy and/or in remission with life expectancy of \< 5 years, with the exception of resected non-melanoma skin cancers, non-muscle invasive bladder cancer, state I head and neck cancer, or stage I colorectal cancer
  • Significant medical condition other than cancer, that would prevent consistent and compliant participation in the study that would, in the opinion of the investigator, make this protocol unreasonably hazardous including but not limited to:
  • Any medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone once daily
  • Active infection requiring systemic therapy
  • History of gastrointestinal disordered (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
  • Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg); subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment (systolic BP \< 160 mmHg or diastolic BP \<95 mmHg)
  • Active or symptomatic viral hepatitis of chronic liver disease
  • Acute or chronic hepatitis B or hepatitis C infection. (Hepatitis B and C testing are not mandatory)
  • Presence of hepatitis B surface antibody is acceptable
  • Human immunodeficiency virus (HIV)-positive subjects with 1 or more of the following:
  • Not receiving highly active anti-retroviral therapy. A change in anti-retroviral therapy within 6 months of the start of screening (except if, after consultation with the principal investigator (PI) / sponsor, a change is made to avoid a potential drug-drug interaction with the study drug).
  • Receiving anti-retroviral therapy that may interfere with the study drug(s) (consult the PI / sponsor for review of medication prior to enrollment).
  • CD4 count \< 350 cell/mm^3 at screening. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
  • History of pituitary or adrenal dysfunction
  • History of hypogonadism
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of \<50% at baseline, or clinically significant ventricular arrhythmias within 6 months prior to treatment start.
  • History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness \</= 1 year prior to treatment start; brain arteriovenous malformation; or intracranial masses such as schawnnomas and meningiomas that are causing edema or mass effect)
  • Uncontrolled diabetes mellitus
  • History of inflammatory bowel disease
  • Baseline moderate and severe hepatic impairment (Child Pugh Class B \& C)
  • Use of any prohibited concomitant medications within 14 days prior to treatment start, or use of prohibited concomitant medication listed in section 7.9.1 within the outlined windows NOTE: Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to treatment start
  • Pre-existing condition that warrants long-term corticosteroid use in excess of 10 mg prednisone/prednisolone daily
  • Known allergies, hypersensitivity or intolerance to apalutamide, abiraterone acetate, prednisone, or GnRH agonist or GnRH antagonist (Allergies or hypersensitivity to abiraterone and/or prednisone would not be applicable to subjects enrolling to B2 expansion).
  • Administration of an investigational therapeutic within 30 days of treatment start
  • Patients that cannot tolerate MRI
  • Any condition which, in the opinion of the investigator, would preclude participation in this trial

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Memorial Sloan Kettering Commack (Limited Protocol Activities)

    Commack, New York, 11725

  • Northwestern University

    Evanston, Illinois, 60208

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

The purpose of this study is to test if treatment with medications that reduce the male hormone level in the participant's body for a few months before surgery can shrink prostate cancer as much as possible, which might reduce the chances of the cancer coming back in the future. These treatments include a hormone injection given monthly or every three months and the study drugs, which include abiraterone acetate, prednisone, and apalutamide.

These medications are being used in combination with surgery and maybe radiotherapy because studies have shown that any single approach on its own is not sufficient to control or get rid of the cancer especially if they have high risk or aggressive features. The researchers hope to learn if combining the study drugs with surgery and radiation will get rid of the cancer from participants' prostates and reduce their prostate-specific antigen (PSA) to an undetectable level.

Conditions
Prostate Cancer
Being tested
Apalutamide, Abiraterone Acetate, Prednisone, GnRH agonist/antagonist
Keywords
prostate cancer, apalutamide, abiraterone acetate, memorial sloan kettering cancer center, 17-646
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 ARN-509, ERLEADA™

    240mg daily orally

  • Abiraterone AcetateDrug

    Also called ZYTIGA

    1000mg daily orally

  • PrednisoneDrug

    5mg BID orally

  • GnRH agonist/antagonistDrug

    Physician's choice, for a total duration not to extend beyond the treatment phase of the protocol or 10 months from the start of investigational agent(s)

Study groups in NCT03436654
Study groupRoleWhat they receive
Cohort A, Treatment 1 (ADT + Apalutamide Only)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: GnRH agonist/antagonist
Cohort A, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)ExperimentalThis arm is no longer being assigned to subjects.
Receives: Drug: Apalutamide; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: GnRH agonist/antagonist
Cohort B1, Treatment 1 (ADT + Apalutamide Only)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: Prednisone
Cohort B1, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: GnRH agonist/antagonist
Cohort B2, Treatment 1 (ADT + Apalutamide Only)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: Prednisone
Cohort B2, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: GnRH agonist/antagonist
B2 Expansion, Treatment 1 (ADT + Apalutamide Only)ExperimentalNot described
Receives: Drug: Apalutamide; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Response (pCR + MRD) in the RP specimen

    The primary efficacy measure of pathological complete response (pCR) and minimal residual disease (MRD) is defined as the less than or equal to 5 mm of morphologically identifiable carcinoma in the RP specimen.

    Measured: 6 months

Secondary outcomes (2)

  1. Rate of undetectable PSA level following Testosterone recovery at 24 months from the time of randomization

    Proportion of patients at 24 months post start of treatment who have an undetectable PSA (defined as < 0.1 ng/mL) and Testosterone Recovery (T>150 ng/dL)

    Measured: 24 months

  2. Time to and frequency of testosterone recovery

    Testosterone rates will be measured at 12 and 24 months from the start of randomization.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2018
  2. Study start21 Jun 2018
  3. Primary completion16 Mar 2026
  4. Study completion14 Feb 2027 (estimated)

Resources

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
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03436654
Sponsor's protocol ID
17-646
Other IDs
PCCTC #: c16-183
Status last verified
Apr 2026
First submitted
7 Feb 2018
Last updated
27 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Apalutamide, Abiraterone Acetate and Prednisone in people with Prostate Cancer, run by Memorial Sloan Kettering Cancer Center at 11 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 46 inclusion and 33 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: under way, not looking for participants, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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?

This study is still under way. Results are not available in the source record yet.

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?

Pathologic Response (pCR + MRD) in the RP specimen (time frame: 6 months). 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 NCT03436654.

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 27 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in