Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)

NCT03141671 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 16-623
• Study Type: interventional
• Target: 345
• Locations: 1 country
• Sites: 8

Brief Summary

This research study is comparing two different combinations of androgen deprivation therapy (ADT) used together with radiation as a treatment for rising PSA after radical prostatectomy (prostate cancer).

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• PSA Progression Free Survival

  Time from randomization to PSA failure or death due to any cause

  Up to 5 years

Secondary Outcomes (11)

• Metastasis Free Survival on conventional imaging or pathologically (MFS)

  Up to 5 years

• Metastasis Free Survival only visible by PET Imaging (MFS-PET)

  Up to 5 years

• Cause Specific Survival

  Up to 5 years

• Overall Survival

  Up to 5 years

• Time to Testosterone Recovery

  Up to 5 years

Study Arms (2)

GnRH + Bicalutamide

EXPERIMENTAL

* GnRH agonist injection monthly or every 3 months for 6 months * Bicalutamide by mouth once/day for 6 months * Salvage radiation (starting 4-10 weeks after initiation of ADT)

Drug: GnRH; Drug: Bicalutamide; Radiation: Salvage radiation

GnRH+Abiraterone+Apalutamide+Prednisone

EXPERIMENTAL

* GnRH agonist injection monthly or every 3 months for 6 months * Abiraterone acetate by mouth once/day for 6 months * Prednisone by mouth once/day for 6 months * Apalutamide by mouth once/day for 6 months * Salvage radiation (starting 4-10 weeks after initiation of ADT)

Drug: GnRH; Radiation: Salvage radiation; Drug: Abiraterone; Drug: Prednisone; Drug: Apalutamide

Interventions

GnRH DRUG

-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread

Also known as: LHRHA

GnRH + Bicalutamide; GnRH+Abiraterone+Apalutamide+Prednisone

Bicalutamide DRUG

-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread

Also known as: Casodex

GnRH + Bicalutamide

Salvage radiation RADIATION

Radiation

GnRH + Bicalutamide; GnRH+Abiraterone+Apalutamide+Prednisone

Abiraterone DRUG

-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread

Also known as: Zytiga

GnRH+Abiraterone+Apalutamide+Prednisone

Prednisone DRUG

Prednisone is a corticosteroid. It prevents the release of substances in the body that cause inflammation. It also suppresses the immune system.

Also known as: Deltasone

GnRH+Abiraterone+Apalutamide+Prednisone

Apalutamide DRUG

-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread

Also known as: ARN-509

GnRH+Abiraterone+Apalutamide+Prednisone

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate cancer
• PSA ≥ 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below.
• Gleason 8-10
• PSA \> 0.5
• Pathologically positive lymph nodes
• pT3 or pT4
• PSA doubling time (DT) \< 10 months
• Negative margins
• Persistent PSA after RP (PSA never dropped below 0.1 after RP)
• Local/regional recurrence on imaging
• Decipher "High risk" (a Medicare-reimbursed test for risk of metastases after prostatectomy)
• Candidate for salvage radiation and ADT treatment
• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and willingness to sign the written informed consent document.
• ≤ Age ≤ 95 at the time of consent
• ECOG Performance Status ≤ 2 (Appendix A)

You may not qualify if:

• Use of post-prostatectomy ADT for \> 30 continuous days prior to registration (ADT defined as use of GnRH agonist, with or without an anti-androgen). However, patients with testosterone recovery after post-prostatectomy ADT are eligible (testosterone recovery defined as total testosterone \> 190 ng/dL) regardless of how long they have been on ADT.
• Prior pelvic radiation unless additional radiation can be safely delivered according to the treating physician
• PSA \> 15 ng/mL in screening
• History of any of the following:
• Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Current evidence of any of the following:
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption
• Active infection (e.g., human immunodeficiency virus \[HIV\] or viral hepatitis)
• Any chronic medical condition requiring a dose of corticosteroid higher than 10 mg prednisone/prednisolone once daily
• Any condition that, in the opinion of the site investigator, would preclude participation in this study
• Moderate or severe hepatic impairment (Child Pugh Class B or C)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Pharmaceutica: collaborator

Study Sites (8)

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute/Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Gonadotropin-Releasing Hormone; bicalutamide; abiraterone; Abiraterone Acetate; Prednisone; apalutamide

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)

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; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Paul Nguyen, MD

  Dana-Farber/Brigham and Women's Cancer Center

  PRINCIPAL INVESTIGATOR

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: Paul Nguyen, MD

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 5, 2017
• Study Start: November 24, 2017
• Primary Completion: April 5, 2025
• Study Completion: December 31, 2025
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)