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Testing the Addition of the Drugs, Apalutamide and Abiraterone with Prednisone, to the Usual Hormone Therapy and Radiation Therapy after Surgery for Prostate Cancer

Trial Status: Active

This phase III trial studies whether adding apalutamide, abiraterone acetate, and prednisone to the usual treatment improves outcome in patients with lymph node positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or reduce the growth of prostate cancer cell growth by blocking the attachment of androgen to its receptors on cancer cells, a mechanism similar to stopping the entrance of a key into its lock. Abiraterone acetate blocks some of the enzymes needed for androgen production and may cause the death of prostate cancer cells dependent on androgen for their growth. Prednisone may help abiraterone acetate work better by making tumor cells more sensitive to the drug. Adding apalutamide and abiraterone acetate with prednisone to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading and extend time without disease spreading compared to the usual approach.

Inclusion Criteria

  • Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
  • Any T-stage is eligible
  • Appropriate stage for study entry based on fluciclovine F-18 positron emission tomography (PET) scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease; (Note that though every effort should be made to obtain a fluciclovine F-18 PET [FACBC, Axumin] scan, if the patient has already had a recent gallium Ga 68-labeled PSMA-11 [Ga-68 PSMA] PET scan or C-11 or F-18 choline PET scan within 90 days prior to registration [to include scan report] then repeat molecular imaging with a fluciclovine F-18 PET [FACBC, Axumin] scan will not be required.)
  • Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen (including external iliacs, internal iliacs, and/or obturator nodes)
  • History/physical examination within 90 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
  • Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA > 0 ng/mL at least 30 days after prostatectomy and within 90 days of registration and before start of GnRH agonist/antagonist
  • Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 45 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =< 45 days and stopped prior to registration)
  • Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
  • Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
  • Serum potassium >= 3.5 mmol/L within 90 days prior to registration
  • Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 90 days prior to registration)
  • Serum albumin >= 3.0 g/dL (within 90 days prior to registration)
  • Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
  • The patient must agree 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 agree 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
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for < 3 years must contact the principal investigator, Ron Chen, Doctor of Medicine (MD)
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria

  • Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. fluciclovine F-18 PET, PSMA, F-18 choline 11)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
  • Didanosine (DDI) antiretroviral therapy is not permitted
  • History of any of the following: * Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy) * Severe or unstable angina, myocardial infarction, 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 registration * New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.) * History of any condition that in the opinion of the investigator, would preclude participation in this study
  • Current evidence of any of the following: * Known gastrointestinal disorder affecting absorption of oral medications * Active uncontrolled infection * Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment * Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily * Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C) * Inability to swallow oral pills * Any current condition that in the opinion of the investigator, would preclude participation in this study
  • Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study

Delaware

Newark
Christiana Care Health System-Christiana Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 302-623-4450
Helen F Graham Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 302-623-4450
Medical Oncology Hematology Consultants PA
Status: ACTIVE
Contact: Site Public Contact
Phone: 302-623-4450

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-851-7115
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-778-1868
Grady Health System
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-489-9164

Illinois

Chicago
Northwestern University
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-695-1301
University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-355-3046
Danville
Carle on Vermilion
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
DeKalb
Northwestern Medicine Cancer Center Kishwaukee
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-352-5360
Effingham
Carle Physician Group-Effingham
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Geneva
Northwestern Medicine Cancer Center Delnor
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-352-5360
Mattoon
Carle Physician Group-Mattoon / Charleston
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-226-4357
New Lenox
UC Comprehensive Cancer Center at Silver Cross
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222
Orland Park
University of Chicago Medicine-Orland Park
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222
Urbana
Carle Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Warrenville
Northwestern Medicine Cancer Center Warrenville
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-352-5360

Indiana

Richmond
Reid Health
Status: ACTIVE
Contact: Site Public Contact
Phone: 937-528-2900

Iowa

Ames
McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-239-4734
Des Moines
Iowa Lutheran Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-241-8704
Iowa Methodist Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-241-6727
Medical Oncology and Hematology Associates-Des Moines
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-282-2921
West Des Moines
Methodist West Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-343-1000

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Overland Park
University of Kansas Cancer Center-Overland Park
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671

Louisiana

Metairie
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 504-210-3539

Maine

Brewer
Lafayette Family Cancer Center-EMMC
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-987-3005

Minnesota

Saint Cloud
Coborn Cancer Center at Saint Cloud Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-229-4907

Missouri

Creve Coeur
Siteman Cancer Center at West County Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Kansas City
University of Kansas Cancer Center - North
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Lee's Summit
University of Kansas Cancer Center - Lee's Summit
Status: ACTIVE
Contact: Site Public Contact
Phone: 913-588-3671
Saint Louis
Siteman Cancer Center-South County
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606
Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606

Montana

Billings
Billings Clinic Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-996-2663

New Jersey

Livingston
Saint Barnabas Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 973-322-2934
New Brunswick
Rutgers Cancer Institute of New Jersey
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-7356
Newark
Rutgers New Jersey Medical School
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-7356

New York

Rochester
Highland Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-341-8113
University of Rochester
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-275-5830

Ohio

Cleveland
Cleveland Clinic Cancer Center / Fairview Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Cleveland Clinic Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-293-5066
Findlay
Armes Family Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 937-528-2900
Mansfield
Cleveland Clinic Cancer Center Mansfield
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Mayfield Heights
Hillcrest Hospital Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Sandusky
North Coast Cancer Care
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Strongsville
Cleveland Clinic Cancer Center Strongsville
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100
Wooster
Cleveland Clinic Wooster Family Health and Surgery Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-271-8777

Oregon

Gresham
Legacy Mount Hood Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 503-413-2150
Portland
Legacy Good Samaritan Hospital and Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-220-4937

Pennsylvania

Chadds Ford
Christiana Care Health System-Concord Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 302-623-4450
West Reading
Reading Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 610-988-9323

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Site Public Contact
Phone: 214-648-7097

Washington

Vancouver
Legacy Salmon Creek Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 503-413-2150

PRIMARY OBJECTIVE:

I. Compare metastasis-free survival (MFS) of salvage radiation therapy (RT) and gonadotropin releasing hormone (GnRH) agonist/antagonist versus (vs.) RT/GnRH agonist/antagonist with abiraterone acetate with prednisone and apalutamide for patients with pathologic node-positive prostate cancer after radical prostatectomy with detectable prostate-specific antigen (PSA).

SECONDARY OBJECTIVES:

I. Compare health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]-26, EuroQol [EQ]-5 Dimension [D]-5 Level [L]), Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]-Fatigue) among the treatment arms.

II. Compare overall survival, biochemical progression-free survival, time to local-regional progression, time to castrate resistance, and cancer-specific survival among the treatment arms.

III. Compare the short-term and long-term treatment-related adverse events among the treatment arms.

EXPLORATORY OBJECTIVES:

I. Validate Decipher score for an exclusively node-positive population and use additional genomic information from Affymetrix Human Exon 1.0st array to develop and validate novel prognostic and predictive biomarkers.

II. Validate the PAM50-based classification of prostate cancer into luminal A, luminal B, and basal subtypes as prognostic markers and determine whether the luminal B subtype is a predictive marker for having a larger improvement in outcome from the addition of abiraterone acetate with prednisone and apalutamide.

III. To optimize quality assurance methodologies and processes for radiotherapy and imaging with machine learning strategies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care hormone therapy per physician discretion for 24 months. Patients also undergo standard of care pelvis and prostate bed radiation therapy 5 days per week over 7-8 weeks beginning within 56 days after first hormone injection if the injection is not started prior to registration or within 90 days after first hormone injection if the injection is started prior to registration in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo standard of care hormone therapy and radiation therapy as in Arm I. Patients also receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD or twice daily (BID) on days 1-90. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years, then annually thereafter.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
NRG Oncology

Principal Investigator
Ronald C. Chen

  • Primary ID NRG-GU008
  • Secondary IDs NCI-2019-06838
  • Clinicaltrials.gov ID NCT04134260