Clinical Trials /

Conventional ADT w/ or w/Out Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT

NCT03777982

Description:

This research study is being offered to those patients who have already received radiation therapy and who are receiving long-term hormonal therapy for their prostate cancer and whose PSA remains detectable (greater than 0.1) despite having received at least 6, but no more than 8 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

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Conventional ADT w/ or w/Out Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 18-530
  • NCT ID: NCT03777982

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
PrednisoneDeltasonePrednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
ApalutamideARN-509Prednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
Abiraterone AcetateZytigaPrednisone+Apalutamide+Abiraterone Acetate +LHRH Agonist
LHRH Agonist or AntagonistGnRHLHRH Agonist or Antagonist

Purpose

This research study is being offered to those patients who have already received radiation therapy and who are receiving long-term hormonal therapy for their prostate cancer and whose PSA remains detectable (greater than 0.1) despite having received at least 6, but no more than 8 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).
    

Trial Arms

NameTypeDescriptionInterventions
LHRH Agonist or AntagonistExperimental-LHRH agonist or antagonist should be prescribed per standard of care
  • LHRH Agonist or Antagonist
Prednisone+Apalutamide+Abiraterone Acetate +LHRH AgonistExperimentalLHRH 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
  • Prednisone
  • Apalutamide
  • Abiraterone Acetate
  • LHRH Agonist or Antagonist

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> 0.1 after radiation and at least 6, but not more than 8 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 or radiographic T3,
                  Gleason 8-10, or PSA > 20 ng/mL, 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:

             --CrCl2 ≥ 45 mL/min

          -  Hepatic and Other:

               -  Bilirubin3 ≤ 1.5 × upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) < 2.5 × ULN

               -  Alanine aminotransferase (ALT) < 2.5 × ULN

               -  Serum Albumin > 3.0 g/dL

               -  Serum potassium ≥ 3.5 mmol/L

          -  Coagulation:

             --International Normalized Ratio (INR) or Prothrombin Time (PT)

          -  Activated Partial Thromboplastin Time

          -  (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular
             weight heparin)

               -  Independent of transfusion and/or growth factors within 3 months prior to
                  randomization

               -  Cockcroft-Gault formula will be used to calculate creatinine clearance

               -  In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure
                  direct and indirect bilirubin; if direct bilirubin is ≤1.5 × ULN, subject may be
                  eligible

          -  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.

          -  Ability to understand and comply with study procedures for the entire length of the
             study as determined by the site investigator or protocol designee

          -  Medications known to lower the seizure threshold (section 5.4.4) must be discontinued
             or substituted prior to C1D1 of study treatment for patients on Arm 2

          -  Able to swallow pills

        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 (systolic blood pressure ≥ 140 mmHg or diastolic blood
                  pressure ≥ 90 mmHg). 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)

          -  Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment (section
             5.4.3). If a strong CYP3A4 inducer must be co-administered, increase the abiraterone
             acetate dosing frequency.

          -  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

          -  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

          -  Individuals with a history of another malignancy are not eligible if the cancer is
             under active treatment or the cancer can be seen on radiology scans or if they are off
             cancer treatment but in the opinion of their oncologist have a high risk of relapse
             within 5 years.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Metastasis Free Survival
Time Frame:2 years
Safety Issue:
Description:the composite of metastasis or any cause death

Secondary Outcome Measures

Measure:PSA nadir
Time Frame:2 years
Safety Issue:
Description:PSA nadir is defined as the lowest PSA after RT completion
Measure:Castrate Resistant PSA Failure Free Survival
Time Frame:2 years
Safety Issue:
Description:Castrate resistant PSA failure is defined as the first PSA increase that is ≥ 25% and 2 ng/mL above the nadir, which is confirmed by a second value 3 or more weeks later, while the serum total testosterone level is < 50 ng/dl (per the PCWG2 criteria).
Measure:Prostate Cancer Specific Survival
Time Frame:2 years
Safety Issue:
Description:Prostate cancer specific survival is defined the time from randomization to death from prostate cancer where death due to other causes are considered as competing risk, or censored at the last date of follow up in living patients.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall survival is defined as the time from randomization to death from any cause with men censored at time of last follow up if alive.
Measure:Disease Free Survival
Time Frame:2 years
Safety Issue:
Description:Disease free survival is measured from the date of randomization to the first recorded disease recurrence consisting of castrate resistant PSA failure and/or local, regional or distant failure and death from any cause, whichever comes first, or censored at the date of last disease assessment for those alive and disease recurrence free.
Measure:Toxicity as measured by CTCAE
Time Frame:2 years
Safety Issue:
Description:We will measure Grade 1-5 toxicities at study visits and follow-up using the CTCAE v.5 forms and determine attribution.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Prostate Cancer

Last Updated

October 15, 2019