Conventional Androgen Deprivation Therapy (ADT) With or Without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT

NCT03777982 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 18-530
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is being offered to those patients who have received radiation therapy and who are receiving long-term hormonal therapy for their prostate cancer and whose PSA remains detectable despite having received at least 6, but no more than 12 months of hormonal therapy. The name of the study drugs involved in this study is:

• LHRHA (luteinizing hormone-releasing hormone agonist or antagonist)
• Abiraterone Acetate
• Apalutamide
• Prednisone

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Metastasis Free Survival

  the composite of metastasis or any cause death

  2 years

Secondary Outcomes (5)

• PSA Nadir

  2 years

• Castrate Resistant PSA Failure Free Survival

  2 years

• Prostate Cancer Specific Survival

  2 years

• Overall Survival

  2 years

• Disease Free Survival

  2 years

Study Arms (2)

LHRH Agonist or Antagonist

EXPERIMENTAL

-LHRH agonist or antagonist should be prescribed per standard of care

Drug: LHRH Agonist or Antagonist

Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist

EXPERIMENTAL

* LHRH agonist or antagonist should be prescribed per standard of care * Abiraterone acetate will be taken once daily * Prednisone will be taken twice daily * Apalutamide will be taken once daily

Drug: Prednisone; Drug: Apalutamide; Drug: Abiraterone Acetate; Drug: LHRH Agonist or Antagonist

Interventions

Prednisone DRUG

Taking advantage of the anti-inflammatory properties of the medication, corticosteroids are used to decrease the swelling around tumors.

Also known as: Deltasone

Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist

Apalutamide DRUG

Apalutamide also prevents the androgens from working within the prostate cancer cells, and can ultimately lead to cancer cell death.

Also known as: ARN-509

Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist

Abiraterone Acetate DRUG

Abiraterone acetate interferes with an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and is required as part of the body's androgen producing process. Because of this interference the amount of androgens produced are decreased. Abiraterone acetate, blocks androgen production at three sources; the testes, the adrenal glands, as well as from the tumor itself

Also known as: Zytiga

Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist

LHRH Agonist or Antagonist DRUG

Luteinizing hormone-releasing hormone (LHRH) agonists (also called LHRH analogs or GnRH agonists) are drugs that lower the amount of testosterone made by the testicles

Also known as: GnRH

LHRH Agonist or Antagonist; Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist

Eligibility Criteria

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

You may qualify if:

• In order to ensure a homogenous population at study entry, a bone scan and not a PET will be used to ensure M0 high risk prostate cancer. A bone scan is to be done up to 6 months prior to the start of initial ADT therapy or up to one month after initiation of ADT to rule out bony metastatic disease.
• Histologically confirmed prostate cancer
• PSA\> undetectable (any value at or above the lower limit of detection for the assay used) after radiation and at least 6, but not more than 12 months of conventional ADT (LHRH agonist or antagonist with or without oral anti androgens, excluding abiraterone acetate and apalutamide) in patients with non-metastatic high risk or N1 prostate cancer
• High risk is defined per the NCCN guidelines - clinical, radiographic, or pathological (biopsy proven) T3 or higher, Gleason 8-10, PSA \> 20 ng/mL, the presence of intraductal, ductal, or cribriform features with any Gleason score, and can be N0 or N1
• A month is defined as 28 days
• 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 ≥18 at the time of consent
• ECOG Performance Status ≤ 2 (Appendix A)
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 3 months of registration.
• System Laboratory Value
• Hematological:
• Platelet count (plt)1 ≥ 100,000/ µL
• Hemoglobin (Hgb)1 ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1000 cells/µL
• Renal:

You may not qualify if:

• Prior radical prostatectomy (excluding TURP and simple prostatectomy)
• 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 (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Known current evidence of any of the following:
• Uncontrolled hypertension. Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
• Gastrointestinal disorder affecting absorption
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Known active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in subjects with positive hepatitis B core antibody prior to first treatment start.
• Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
• 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 steroids or inhaled corticosteroids are permitted.
• Any condition that, in the opinion of the site investigator, would preclude participation in this study
• Baseline moderate or severe hepatic impairment (ChildPugh Class B or C)
• Patients who are currently receiving treatment with a prohibited medication according to Section 5.4 (Tables 2 and 3), must discontinue that medication prior to starting treatment and must not restart for the duration of the study if randomized to ARM 2.
• Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate

Sponsors & Collaborators

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

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Prednisone; apalutamide; Abiraterone Acetate; Gonadotropin-Releasing Hormone

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)

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

Results Point of Contact

• Title: Anthony D'Amico
• Organization: Dana Farber/Mass General Brigham Cancer Care

adamico@bwh.harvard.edu

857-215-1489

Study Officials

• Anthony D'Amico, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: April 20, 2020
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Requests may be directed to: \[contact information for Sponsor-Investigator or designee\].

Locations

US (5)