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

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ClinicalTrials.gov Identifier: NCT03141671
Recruitment Status : Recruiting
First Posted : May 5, 2017
Last Update Posted : July 5, 2019
Sponsor:
Collaborator:
Janssen Pharmaceutica
Information provided by (Responsible Party):
Paul Nguyen, MD, Dana-Farber Cancer Institute

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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: GnRH Drug: Bicalutamide Radiation: Salvage radiation Drug: Abiraterone Drug: Prednisone Drug: Apalutamide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 345 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 24, 2017
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: GnRH + Bicalutamide
  • 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
-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread
Other Name: LHRHA

Drug: Bicalutamide
-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread
Other Name: Casodex

Radiation: Salvage radiation
Radiation

Experimental: GnRH+Abiraterone+Apalutamide+Prednisone
  • 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
-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread
Other Name: LHRHA

Radiation: Salvage radiation
Radiation

Drug: Abiraterone
-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread
Other Name: Zytiga

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

Drug: Apalutamide
-blocks the function of hormones including testosterone which prostate cancer uses to grow and spread
Other Name: ARN-509




Primary Outcome Measures :
  1. PSA Progression Free Survival [ Time Frame: Up to 5 years ]
    Time from randomization to PSA failure, confirmed by a second reading, or death due to any cause


Secondary Outcome Measures :
  1. Metastasis Free Survival [ Time Frame: Up to 5 years ]
    Time from randomization to distant metastasis or death due to any cause or censored at date last known alive.

  2. Cause Specific Survival [ Time Frame: Up to 5 years ]
    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.

  3. Overall Survival [ Time Frame: Up to 5 years ]
    Time from randomization to death due to any cause or censored at date last known alive

  4. Time to Testosterone Recovery [ Time Frame: Up to 5 years ]
    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

  5. Toxicity as measured by CTCAE v.4.0 [ Time Frame: Up to 5 years ]
    Measure Grade 1-5 toxicities at study visits and follow-up using the CTCAE v.4.0 forms and determine attribution

  6. Time to reinitiation of ADT [ Time Frame: Up to 5 years ]
    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.

  7. Patient reported QOL [ Time Frame: Up to 5 years ]
    Patient-reported Quality of Life will be measured by a fatigue questionnaire

  8. Patient reported QOL [ Time Frame: Up to 5 years ]
    Patient-reported Quality of Life will be measured by a questionnaire assessing symptoms related to prostate cancer

  9. Patient reported QOL [ Time Frame: Up to 5 years ]
    Patient-reported Quality of Life will be measured by a memory survey

  10. Cardiovascular events consisting of myocardial infarction [ Time Frame: Up to 5 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03141671


Contacts
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Contact: Amanda Whitbeck 617-582-8939 awhitbeck@bwh.harvard.edu
Contact: Paul Nguyen, MD 617-732-7936 PNGUYEN@lroc.harvard.edu

Locations
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United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92093
Contact: Brent Rose, MD    858-822-5398    bsrose@ucsd.edu   
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Felix Feng, MD    415-476-1907    Felix.Feng@ucsf.edu   
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: James Yu, MD    203-737-5801    james.b.yu@yale.edu   
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Russell Szmulewitz, MD    773-834-0591    mailto:rszmulew@medicine.bsd.uchicago.edu   
United States, Massachusetts
Dana-Farber Cancer Institute/Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Paul Nguyen, MD    617-732-7936    PNGUYEN@lroc.harvard.edu   
Principal Investigator: Paul Nguyen, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Daniel Spratt, MD       mailto:sprattda@umich.edu   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Marissa Kollmeier, MD    212-639-6756    mailto:KollmeiM@mskcc.org   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Karen Hoffman, MD    713-563-2361    • KHoffman1@mdanderson.org   
Sponsors and Collaborators
Dana-Farber Cancer Institute
Janssen Pharmaceutica
Investigators
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Principal Investigator: Paul Nguyen, MD Brigham and Women's Hospital/Dana-Farber Cancer Institute
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Responsible Party: Paul Nguyen, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03141671    
Other Study ID Numbers: 16-623
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Paul Nguyen, MD, Dana-Farber Cancer Institute:
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Bicalutamide
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists