A Randomized Phase III Study - Conventional Androgen Deprivation Therapy With or Without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and Androgen Deprivation Therapy
Overview
- Phase
- Phase 3
- Intervention
- LHRH Agonist or Antagonist
- Conditions
- Prostate Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 12
- Locations
- 5
- Primary Endpoint
- Metastasis Free Survival
- Status
- Terminated
- Last Updated
- last year
Overview
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
Detailed Description
This research study is a Phase III clinical trial. Phase III clinical trials test the effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that an intervention is being studied. In this study, the investigational agents are apalutamide and abiraterone acetate. Abiraterone acetate (used in combination with prednisone) is an FDA (the U.S. Food and Drug Administration) approved drug for prostate cancer, but is approved in patients that have prostate cancer spread to other parts of their body and have been previously treated with ADT. Apalutamide has also been approved by the FDA for men whose cancer does not respond to hormone therapy but it is still investigational for this type of cancer. In this research study, the investigators are looking at two methods of androgen deprivation therapy (ADT), also known as hormonal therapy, to determine which method is better for improving long term cure rates. ADT blocks the function of hormones, including testosterone which prostate cancer uses to grow and spread. The first method of ADT includes prednisone, apalutamide, and abiraterone acetate plus standard ADT and the second method of ADT is standard ADT alone for men with this type of prostate cancer. Currently, the best standard treatment for men with this type of prostate cancer includes standard ADT. All participants in this study will receive the main standard form of ADT called a luteinizing hormone-releasing hormone agonist or antagonist (LHRHA).
Investigators
Anthony V. D'Amico, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
LHRH Agonist or Antagonist
-LHRH agonist or antagonist should be prescribed per standard of care
Intervention: LHRH Agonist or Antagonist
Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
* 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
Intervention: Prednisone
Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
* 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
Intervention: Apalutamide
Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
* 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
Intervention: Abiraterone Acetate
Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
* 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
Intervention: LHRH Agonist or Antagonist
Outcomes
Primary Outcomes
Metastasis Free Survival
Time Frame: 2 years
the composite of metastasis or any cause death
Secondary Outcomes
- 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)