Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma
2 other identifiers
interventional
102
1 country
11
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 prostate-cancer
Started Jun 2018
Longer than P75 for phase_2 prostate-cancer
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 7, 2018
CompletedFirst Posted
Study publicly available on registry
February 19, 2018
CompletedStudy Start
First participant enrolled
June 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 16, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 14, 2027
ExpectedApril 27, 2026
April 1, 2026
7.7 years
February 7, 2018
April 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
6 months
Secondary Outcomes (2)
Rate of undetectable PSA level following Testosterone recovery at 24 months from the time of randomization
24 months
Time to and frequency of testosterone recovery
24 months
Study Arms (7)
Cohort A, Treatment 1 (ADT + Apalutamide Only)
EXPERIMENTALCohort A, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)
EXPERIMENTALThis arm is no longer being assigned to subjects.
Cohort B1, Treatment 1 (ADT + Apalutamide Only)
EXPERIMENTALCohort B1, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)
EXPERIMENTALCohort B2, Treatment 1 (ADT + Apalutamide Only)
EXPERIMENTALCohort B2, Treatment 2 (ADT + Apalutamide + Abiraterone Acetate + Prednisone)
EXPERIMENTALB2 Expansion, Treatment 1 (ADT + Apalutamide Only)
EXPERIMENTALInterventions
1000mg daily orally
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)
5mg BID orally
240mg daily orally
Eligibility Criteria
You may qualify if:
- 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
- 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.
- 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)
- 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
- +28 more criteria
You may not qualify if:
- 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
- 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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
University of Chicago
Chicago, Illinois, 60637, United States
Northwestern University
Evanston, Illinois, 60208, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Dallos, MD
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 7, 2018
First Posted
February 19, 2018
Study Start
June 21, 2018
Primary Completion
March 16, 2026
Study Completion (Estimated)
February 14, 2027
Last Updated
April 27, 2026
Record last verified: 2026-04