Clinical Trials /

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

NCT03141671

Description:

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).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)
  • Official Title: Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone Acetate and Apalutamide (ARN-509) for Rising PSA After Radical Prostatectomy With Adverse Features.(FORMULA-509 Trial)

Clinical Trial IDs

  • ORG STUDY ID: 16-623
  • NCT ID: NCT03141671

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
GnRHLHRHAGnRH + Bicalutamide
BicalutamideCasodexGnRH + Bicalutamide
AbirateroneZytigaGnRH+Abiraterone+Apalutamide+Prednisone
PrednisoneDeltasoneGnRH+Abiraterone+Apalutamide+Prednisone
ApalutamideARN-509GnRH+Abiraterone+Apalutamide+Prednisone

Purpose

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).

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and 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.

      Currently, the best standard treatment for men with this type of prostate cancer includes
      radiation therapy combined with androgen deprivation therapy (ADT). ADT blocks the function
      of hormones including testosterone which prostate cancer uses to grow and spread. All
      participants in this study will receive the main standard form of ADT called a luteinizing
      hormone-releasing hormone agonist (LHRHA). Physicians often also use another drug called
      bicalutamide to help the LHRHA block hormone function. The investigators are testing whether
      using two newer anti-hormonal drugs called abiraterone acetate and apalutamide with LHRHA can
      improve cure rates compared to using bicalutamide plus LHRHA. These two drugs work together
      to suppress both testosterone and the receptor where testosterone binds thereby providing
      more potent hormone suppression.
    

Trial Arms

NameTypeDescriptionInterventions
GnRH + BicalutamideExperimentalGnRH 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)
  • GnRH
  • Bicalutamide
GnRH+Abiraterone+Apalutamide+PrednisoneExperimentalGnRH 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)
  • GnRH
  • Abiraterone
  • Prednisone
  • Apalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  18 ≤ Age ≤ 95 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) ≥ 100,000/ µL

               -  Hemoglobin (Hgb) ≥ 9 g/dL

               -  Absolute neutrophil count (ANC) ≥ 1000 cells/µL

          -  Renal:

             --GFR1 ≥ 45 mL/min

          -  Hepatic and Other:

               -  Bilirubin2 ≤ 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)

               -  Cockcroft-Gault formula will be used to calculate creatinine clearance (see study
                  procedure manual SPM)

               -  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 (see list under prohibited meds) must
             be discontinued or substituted at least 4 weeks prior to study entry (Section 5.5)

          -  Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be discontinued prior
             to study entry

          -  Able to swallow pills

        Exclusion Criteria:

          -  Post-prostatectomy use of ADT for > 30 days prior to study entry

          -  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

          -  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

          -  Confirmed bone metastases on imaging
      
Maximum Eligible Age:95 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA Progression Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to PSA failure, confirmed by a second reading, or death due to any cause

Secondary Outcome Measures

Measure:Metastasis Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to distant metastasis or death due to any cause or censored at date last known alive.
Measure:Cause Specific Survival
Time Frame:Up to 5 years
Safety Issue:
Description:The interval from randomization to the date of last known follow-up alive or date of death from each of the following causes: prostate cancer, cardiovascular disease, other causes.
Measure:Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to death due to any cause or censored at date last known alive
Measure:Time to Testosterone Recovery
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to date at which testosterone level returns to a normal level, or censored at the date of last disease evaluation for those whose testosterone has not reached a normal level
Measure:Toxicity as measured by CTCAE v.4.0
Time Frame:Up to 5 years
Safety Issue:
Description:Measure Grade 1-5 toxicities at study visits and follow-up using the CTCAE v.4.0 forms and determine attribution
Measure:Time to reinitiation of ADT
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to date at which ADT is restarted for disease progression. Censoring occurs at date of last disease evaluation for those who are not restarted on ADT.
Measure:Patient reported QOL
Time Frame:Up to 5 years
Safety Issue:
Description:Patient-reported Quality of Life will be measured by a fatigue questionnaire
Measure:Patient reported QOL
Time Frame:Up to 5 years
Safety Issue:
Description:Patient-reported Quality of Life will be measured by a questionnaire assessing symptoms related to prostate cancer
Measure:Patient reported QOL
Time Frame:Up to 5 years
Safety Issue:
Description:Patient-reported Quality of Life will be measured by a memory survey
Measure:Cardiovascular events consisting of myocardial infarction
Time Frame:Up to 5 years
Safety Issue:
Description:Time from randomization to date at which first cardiovascular event (myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) occurs. Censoring occurs at date of last disease evaluation for those who did not have a cardiovascular event.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Prostate Cancer

Last Updated

July 2, 2019