BIOMARKER TRIAL of APALUTAMIDE and RADIATION for RECURRENT PROSTATE CANCER (BALANCE)
PSA Progression, Stage III Prostate Adenocarcinoma, Stage IV Prostate Adenocarcinoma
About this trial
This is an interventional treatment trial for PSA Progression
Eligibility Criteria
Inclusion Criteria:
- Pathologically (histologically) proven diagnosis of prostate adenocarcinoma; prostatectomy must have been performed within 10 years prior to Step 1 registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
Post-prostatectomy patients with a detectable serum PSA (≥ 0.1, but ≤ 1.0 ng/mL) at study entry (within 90 days of Step 1 registration) and at least one of the following:
- Gleason score 7-10 (International Society of Urological Pathology [ISUP] grade group 2 to 5)
ISUP grade group:
- Grade Group 1: Gleason score ≤ 6,
- Grade Group 2: Gleason score 3 + 4 = 7,
- Grade Group 3: Gleason score 4 + 3 = 7,
- Grade Group 4: Gleason score 8,
- Grade Group 5: Gleason scores 9 and 10
- >= T3a disease
- Persistent elevation of PSA after prostatectomy measured within 90 days after surgery (PSA never became undetectable) of > 0.04 but < 0.2 ng/mL (PSA nadir)
- pN0 or pNx
- History/physical examination within 90 days prior to Step 1 registration
- Karnofsky performance status of 70-100 within 90 days prior to Step 1 registration
- Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on Decipher GRID platform; Note: if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation
Prior androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to Step 1 registration and given for ≤ 90 days duration
- For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date
- Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility
- Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
- Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors within 90 days prior to step 1 registration
- Serum albumin ≥ 3.0 g/dL within 90 days prior to Step 1 registration
- Glomerular filtration rate (GFR) ≥ 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to Step 1 registration
- Serum total bilirubin ≤ 1.5 x 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 Step 1 registration
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN within 90 days prior to Step 1 registration
- Testosterone > 50 ng/dL within 90 days prior to Step 1 registration
- Concomitant medications known to lower the seizure threshold discontinued or substituted at least 4 weeks (30 days) prior to Step 1 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
- The patient must agree not to donate sperm during the study treatment and for 3 months after receiving the last dose of study drug
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
- Definitive clinical, radiologic, or pathologic evidence of metastatic disease (M1) or lymph node involvement (N1)
- Prior invasive malignancy (except non-melanomatous skin cancer, carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
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 Step 1 registration)
- History of documented inflammatory bowel disease
- Transmural myocardial infarction within the last 4 months prior to Step 1 registration.
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to Step 1 registration
- 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 (eg, human immunodeficiency virus [HIV] or viral hepatitis)
- Uncontrolled hypertension
- Any current condition that in the opinion of the investigator, would preclude participation in this study
- Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is not allowed
- HIV positive with CD4 count < 200 cells/microliter within 30 days prior to registration
- HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. (Note: HIV testing is not required for eligibility for this protocol as it is self-reported.)
- For patients who have not undergone prior Decipher analysis, submission of the specimen to GenomeDx should be as soon as possible after study registration (Step 1) as these results can take up 21 days after the specimen is received at GenomeDx; Step 2 registration must occur within 6 weeks (42 days) of Step 1 registration; if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation
- Patients must not plan to participate in any other clinical trials while receiving treatment on this study or being followed post-protocol therapy.
Sites / Locations
- Arizona Breast Cancer Specialists-Gilbert
- Arizona Center for Cancer Care-Peoria
- Arizona Breast Cancer Specialists-Scottsdale
- Arizona Center for Cancer Care-Surprise
- University of Arkansas for Medical Sciences
- Alta Bates Summit Medical Center-Herrick Campus
- Marin General Hospital
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Gene Upshaw Memorial Tahoe Forest Cancer Center
- Sutter Solano Medical Center/Cancer Center
- University of Colorado Hospital
- Penrose-Saint Francis Healthcare
- UCHealth Memorial Hospital Central
- Memorial Hospital North
- Poudre Valley Hospital
- Cancer Care and Hematology-Fort Collins
- Valley View Hospital Cancer Center
- UCHealth Greeley Hospital
- Medical Center of the Rockies
- Stamford Hospital/Bennett Cancer Center
- Helen F Graham Cancer Center
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- George Washington University Medical Center
- AdventHealth Altamonte
- Regional Cancer Center-Lee Memorial Health System
- AdventHealth Kissimmee
- AdventHealth Orlando
- AdventHealth East Orlando
- Cleveland Clinic-Weston
- AdventHealth Winter Park
- Grady Health System
- Emory University Hospital Midtown
- Emory University Hospital/Winship Cancer Institute
- Emory Saint Joseph's Hospital
- Northside Hospital
- Augusta University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Luke's Cancer Institute - Boise
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Luke's Cancer Institute - Twin Falls
- Rush University Medical Center
- University of Illinois
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Edward Hines Jr VA Hospital
- Loyola University Medical Center
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- OSF Saint Francis Medical Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Goshen Center for Cancer Care
- Reid Health
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Greater Regional Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Mercy Medical Center-West Lakes
- University of Kansas Cancer Center
- Olathe Health Cancer Center
- University of Kansas Cancer Center-Overland Park
- Salina Regional Health Center
- University of Kansas Hospital-Westwood Cancer Center
- University of Kentucky/Markey Cancer Center
- Mary Bird Perkins Cancer Center
- East Jefferson General Hospital
- LSU Healthcare Network / Metairie Multi-Specialty Clinic
- MaineHealth Coastal Cancer Treatment Center
- Waldo County General Hospital
- MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
- Lafayette Family Cancer Center-EMMC
- Stephens Memorial Hospital
- Maine Medical Center-Bramhall Campus
- Penobscot Bay Medical Center
- MaineHealth Cancer Care Center of York County
- MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
- Maine Medical Center- Scarborough Campus
- Maine Medical Partners - South Portland
- University of Maryland/Greenebaum Cancer Center
- Saint Agnes Hospital
- Central Maryland Radiation Oncology in Howard County
- UM Baltimore Washington Medical Center/Tate Cancer Center
- Lahey Hospital and Medical Center
- Lowell General Hospital
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Saint Joseph Mercy Brighton
- Saint Joseph Mercy Canton
- Saint Joseph Mercy Chelsea
- GenesisCare USA - Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Beaumont Hospital - Dearborn
- Henry Ford Hospital
- Michigan State University Clinical Center
- GenesisCare USA - Farmington Hills
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- West Michigan Cancer Center
- Sparrow Hospital
- Lakeland Hospital Niles
- Spectrum Health Reed City Hospital
- William Beaumont Hospital-Royal Oak
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Munson Medical Center
- William Beaumont Hospital - Troy
- GenesisCare USA - Troy
- Henry Ford West Bloomfield Hospital
- Metro Health Hospital
- Mayo Clinic Health System in Albert Lea
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Mayo Clinic Health Systems-Mankato
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Minneapolis VA Medical Center
- Health Partners Inc
- Monticello Cancer Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud Hospital
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Fairview Lakes Medical Center
- University of Mississippi Medical Center
- Southeast Cancer Center
- Siteman Cancer Center at West County Hospital
- Capital Region Southwest Campus
- Kansas City Veterans Affairs Medical Center
- University of Kansas Cancer Center - North
- University of Kansas Cancer Center - Lee's Summit
- Delbert Day Cancer Institute at PCRMC
- Washington University School of Medicine
- Siteman Cancer Center-South County
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Billings Clinic Cancer Center
- Bozeman Deaconess Hospital
- Benefis Healthcare- Sletten Cancer Institute
- Nebraska Methodist Hospital
- Alegent Health Bergan Mercy Medical Center
- University of Nebraska Medical Center
- Comprehensive Cancer Centers of Nevada - Henderson
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
- Las Vegas Cancer Center-Henderson
- OptumCare Cancer Care at Seven Hills
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- GenesisCare USA - Henderson
- Desert West Surgery
- OptumCare Cancer Care at Charleston
- University Medical Center of Southern Nevada
- Hope Cancer Care of Nevada
- Radiation Oncology Centers of Nevada Central
- GenesisCare USA - Las Vegas
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Radiation Oncology Centers of Nevada Southeast
- Cancer Therapy and Integrative Medicine
- Ann M Wierman MD LTD
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- OptumCare Cancer Care at MountainView
- Comprehensive Cancer Centers of Nevada-Summerlin
- Summerlin Hospital Medical Center
- Las Vegas Cancer Center-Medical Center
- Comprehensive Cancer Centers of Nevada
- GenesisCare USA - Fort Apache
- OptumCare Cancer Care at Fort Apache
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- Comprehensive Cancer Centers of Nevada - Central Valley
- University Cancer Center
- Hope Cancer Care of Nevada-Pahrump
- Radiation Oncology Associates
- New Hampshire Oncology Hematology PA-Concord
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Solinsky Center for Cancer Care
- Virtua Memorial
- Rutgers Cancer Institute of New Jersey
- Sidney Kimmel Cancer Center Washington Township
- Robert Wood Johnson University Hospital Somerset
- University of New Mexico Cancer Center
- New Mexico Oncology Hematology Consultants
- James J Peters VA Medical Center
- New York-Presbyterian/Brooklyn Methodist Hospital
- Sands Cancer Center
- Mary Imogene Bassett Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Wilmot Cancer Institute Radiation Oncology at Greece
- Highland Hospital
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- UNC Lineberger Comprehensive Cancer Center
- Novant Cancer Institute Radiation Oncology - Supply
- Novant Health Cancer Institute Radiation Oncology - Wilmington
- Novant Health New Hanover Regional Medical Center
- Summa Health System - Akron Campus
- Cleveland Clinic Akron General
- UHHS-Chagrin Highlands Medical Center
- Indu and Raj Soin Medical Center
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Geauga Hospital
- University of Cincinnati Cancer Center-UC Medical Center
- Oncology Hematology Care Inc-Kenwood
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- The Mark H Zangmeister Center
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Greater Dayton Cancer Center
- First Dayton Cancer Care
- Kettering Medical Center
- Cleveland Clinic Cancer Center Mansfield
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- University Hospitals Parma Medical Center
- University Hospitals Portage Medical Center
- North Coast Cancer Care
- UH Seidman Cancer Center at Firelands Regional Medical Center
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- University of Cincinnati Cancer Center-West Chester
- UHHS-Westlake Medical Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences Center
- Cancer Treatment Centers of America
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- UPMC Altoona
- UPMC-Heritage Valley Health System Beaver
- Saint Luke's University Hospital-Bethlehem Campus
- Christiana Care Health System-Concord Health Center
- Northeast Radiation Oncology Center
- UPMC Cancer Center at UPMC Horizon
- UPMC Cancer Centers - Arnold Palmer Pavilion
- UPMC Pinnacle Cancer Center/Community Osteopathic Campus
- Penn State Milton S Hershey Medical Center
- UPMC-Johnstown/John P. Murtha Regional Cancer Center
- UPMC Cancer Center at UPMC McKeesport
- UPMC Cancer Center - Monroeville
- UPMC Hillman Cancer Center in Coraopolis
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Jefferson Torresdale Hospital
- UPMC-Magee Womens Hospital
- UPMC-Saint Margaret
- UPMC-Shadyside Hospital
- UPMC-Passavant Hospital
- UPMC-Saint Clair Hospital Cancer Center
- Guthrie Medical Group PC-Robert Packer Hospital
- UPMC Cancer Center at UPMC Northwest
- UPMC Uniontown Hospital Radiation Oncology
- UPMC Washington Hospital Radiation Oncology
- Reading Hospital
- Asplundh Cancer Pavilion
- Prisma Health Cancer Institute - Spartanburg
- Prisma Health Cancer Institute - Faris
- Prisma Health Cancer Institute - Eastside
- Self Regional Healthcare
- Prisma Health Cancer Institute - Greer
- The Radiation Oncology Center-Hilton Head/Bluffton
- Prisma Health Cancer Institute - Seneca
- Rapid City Regional Hospital
- The West Clinic - Wolf River
- Vanderbilt University/Ingram Cancer Center
- UT Southwestern/Simmons Cancer Center-Dallas
- Audie L Murphy VA Hospital
- University of Texas Health Science Center at San Antonio
- American Fork Hospital / Huntsman Intermountain Cancer Center
- Sandra L Maxwell Cancer Center
- Farmington Health Center
- Logan Regional Hospital
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Riverton Hospital
- Saint George Regional Medical Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- LDS Hospital
- Southwestern Vermont Medical Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- Norris Cotton Cancer Center-North
- Naval Medical Center - Portsmouth
- Hunter Holmes McGuire Veterans Administration Medical Center
- PeaceHealth Saint Joseph Medical Center
- Legacy Salmon Creek Hospital
- Providence Saint Mary Regional Cancer Center
- West Virginia University Healthcare
- Camden Clark Medical Center
- Marshfield Medical Center-EC Cancer Center
- Aurora Cancer Care-Grafton
- Aurora BayCare Medical Center
- Aurora Cancer Care-Kenosha South
- Marshfield Medical Center-Marshfield
- Froedtert Menomonee Falls Hospital
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Zablocki Veterans Administration Medical Center
- Marshfield Clinic-Minocqua Center
- Cancer Center of Western Wisconsin
- Vince Lombardi Cancer Clinic - Oshkosh
- Marshfield Medical Center-Rice Lake
- Vince Lombardi Cancer Clinic-Sheboygan
- Marshfield Medical Center-River Region at Stevens Point
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aurora West Allis Medical Center
- Froedtert West Bend Hospital/Kraemer Cancer Center
- Diagnostic and Treatment Center
- Marshfield Medical Center - Weston
- Tom Baker Cancer Centre
- University Health Network-Princess Margaret Hospital
- CIUSSSEMTL-Hopital Maisonneuve-Rosemont
- The Research Institute of the McGill University Health Centre (MUHC)
- CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Arm 1 (Radiation Therapy + Placebo)
Arm 2 (Radiation Therapy + Apalutamide)
Patients undergo external beam radiation therapy on Day 1 for 7.5 weeks. Beginning on Day 1 of radiation therapy, patients receive placebo PO QD on Days 1-30. Treatment repeats every 30 days for up to 6 courses (6 months) in the absence of disease progression or unacceptable toxicity.
Patients undergo external beam radiation therapy on Day 1 for 7.5 weeks. Beginning on Day 1 of radiation therapy, patients receive apalutamide PO QD on Days 1-30. Treatment repeats every 30 days for up to 6 courses (6 months)in the absence of disease progression or unacceptable toxicity.