AzTrials
AzTrials

Prostate AdenocarcinomaPhase 3NCT04134260

Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial

A Phase 3 study testing Apalutamide, Biospecimen Collection and Bone Scan in people with Prostate Adenocarcinoma and Stage I Prostate Cancer AJCC v8, run by NRG Oncology at 350 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

This phase III trial studies whether adding apalutamide 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Apalutamide, Biospecimen Collection and Bone Scan
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
586 participants
Where
350 sitesin 2 countries
Study dates
16 Apr 2020to 1 Nov 2031
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (American Joint Committee on Cancer [AJCC] 8th edition [ed])
  • Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA < 0.20 ng/mL at time of registration, PET scan is recommended but not required
  • Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
  • History/physical examination within 90 days prior to registration
  • Age >= 18
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  • 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
  • Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =< 180 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 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, Ronald Chen, Doctor of Medicine (MD)
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Who cannot join

  • Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, [FACBC, Axumin], F-18 PSMA PET [Pylarify], flotufolastat F-18 PSMA PET scan [Posluma], Gallium-68 PSMA PET scan or C-11 choline PET)
  • 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
  • Androgen deprivation therapy (ADT) prior to radical prostatectomy
  • Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =< 180 days and stopped prior to registration, which is allowed
  • Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
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  • 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 12 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
  • Patients with inflammatory bowel disease

Trial locations and contacts

350 sites in 2 countries.

302 sites in 2 countries

United States300 sites
  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • Alton Memorial Hospital

    Alton, Illinois, 62002

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory Proton Therapy Center

    Atlanta, Georgia, 30308

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Advocate Outpatient Center - Aurora

    Aurora, Illinois, 60506

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • Advocate Good Shepherd Hospital

    Barrington, Illinois, 60010

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Crozer-Keystone Regional Cancer Center at Broomall

    Broomall, Pennsylvania, 19008

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Sands Cancer Center

    Canandaigua, New York, 14424

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Carlisle Regional Cancer Center

    Carlisle, Pennsylvania, 17015

  • Mercy Cancer Center - Carmichael

    Carmichael, California, 95608

  • Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Saint Anthony Regional Hospital

    Carroll, Iowa, 51401

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Duke Cancer Center Cary

    Cary, North Carolina, 27518

  • Saint Luke's Hospital

    Cedar Rapids, Iowa, 52402

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • AMG Crystal Lake - Oncology

    Crystal Lake, Illinois, 60014

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • UM Sylvester Comprehensive Cancer Center at Doral

    Doral, Florida, 33166

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • Delaware County Memorial Hospital

    Drexel Hill, Pennsylvania, 19026

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • Mercy Cancer Center - Elk Grove

    Elk Grove, California, 95758

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • UPMC Cancer Center at UPMC Horizon

    Farrell, Pennsylvania, 16121

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • Northwell Health Physicians Partners Radiation Medicine at Queens

    Forest Hills, New York, 11375

  • Tarrant County Hospital District/JPS Health Network

    Fort Worth, Texas, 76104

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Crozer Regional Cancer Center at Brinton Lake

    Glen Mills, Pennsylvania, 19342

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Bellin Memorial Hospital

    Green Bay, Wisconsin, 54301

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Marin General Hospital

    Greenbrae, California, 94904

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Kaiser Permanente South Bay

    Harbor City, California, 90710

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Advocate South Suburban Hospital

    Hazel Crest, Illinois, 60429

  • Comprehensive Cancer Centers of Nevada - Henderson

    Henderson, Nevada, 89052

  • Oncology Las Vegas - Henderson

    Henderson, Nevada, 89074

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • IRMC Cancer Center

    Indiana, Pennsylvania, 15701

  • Kaiser Permanente-Irvine

    Irvine, California, 92618

  • Emory Johns Creek Hospital

    Johns Creek, Georgia, 30097

  • UPMC-Johnstown/John P. Murtha Regional Cancer Center

    Johnstown, Pennsylvania, 15901

  • Freeman Health System

    Joplin, Missouri, 64804

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kansas Cancer Center - Briarcliff

    Kansas City, Missouri, 64116

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • Mid-Michigan Physicians-Lansing

    Lansing, Michigan, 48912

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

  • Radiation Oncology Centers of Nevada Central

    Las Vegas, Nevada, 89106

  • Radiation Oncology Centers of Nevada Southeast

    Las Vegas, Nevada, 89119

  • Comprehensive Cancer Centers of Nevada - Northwest

    Las Vegas, Nevada, 89128

  • Oncology Las Vegas - Tenaya

    Las Vegas, Nevada, 89128

  • OptumCare Cancer Care at MountainView

    Las Vegas, Nevada, 89128

  • Comprehensive Cancer Centers of Nevada - Town Center

    Las Vegas, Nevada, 89144

  • Comprehensive Cancer Centers of Nevada-Summerlin

    Las Vegas, Nevada, 89144

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • Comprehensive Cancer Centers of Nevada - Central Valley

    Las Vegas, Nevada, 89169

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89183

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • AMG Libertyville - Oncology

    Libertyville, Illinois, 60048

  • Condell Memorial Hospital

    Libertyville, Illinois, 60048

  • Cancer Partners of Nebraska

    Lincoln, Nebraska, 68516

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Tibor Rubin VA Medical Center

    Long Beach, California, 90822

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Kaiser Permanente West Los Angeles

    Los Angeles, California, 90034

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • Fairview Clinics and Surgery Center Maple Grove

    Maple Grove, Minnesota, 55369

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

    Mechanicsburg, Pennsylvania, 17050

  • VCU Massey Cancer Center at Hanover Medical Park

    Mechanicsville, Virginia, 23116

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • Mary Bird Perkins Cancer Center - Metairie

    Metairie, Louisiana, 70002

  • East Jefferson General Hospital

    Metairie, Louisiana, 70006

  • LSU Healthcare Network / Metairie Multi-Specialty Clinic

    Metairie, Louisiana, 70006

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Garnet Health Medical Center

    Middletown, New York, 10940

  • Bon Secours Saint Francis Medical Center

    Midlothian, Virginia, 23114

  • Beebe South Coastal Health Campus

    Millville, Delaware, 19967

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Avera Cancer Institute - Mitchell

    Mitchell, South Dakota, 57301

  • UPMC Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • Monticello Cancer Center

    Monticello, Minnesota, 55362

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • UPMC Hillman Cancer Center in Coraopolis

    Moon Township, Pennsylvania, 15108

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • Edward Hospital/Cancer Center

    Naperville, Illinois, 60540

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Rutgers New Jersey Medical School

    Newark, New Jersey, 07101

  • Carle BroMenn Medical Center

    Normal, Illinois, 61761

  • Carle Cancer Institute Normal

    Normal, Illinois, 61761

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • HSHS Saint Elizabeth's Hospital

    O'Fallon, Illinois, 62269

  • Northwestern Medicine Oak Brook

    Oak Brook, Illinois, 60523

  • Drexel Town Square Health Center

    Oak Creek, Wisconsin, 53154

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • Kaiser Permanente-Ontario

    Ontario, California, 91761

  • Northwestern Medicine Orland Park

    Orland Park, Illinois, 60462

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • McLaren Cancer Institute-Owosso

    Owosso, Michigan, 48867

  • Advocate High Tech Medical Park

    Palos Heights, Illinois, 60463

  • Kaiser Permanente - Panorama City

    Panorama City, California, 91402

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • OSF Saint Francis Radiation Oncology at Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Valley Radiation Oncology

    Peru, Illinois, 61354

  • Cancer Center at Saint Joseph's

    Phoenix, Arizona, 85004

  • Avera Cancer Institute at Pierre

    Pierre, South Dakota, 57501

  • UPMC-Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UPMC-Saint Clair Hospital Cancer Center

    Pittsburgh, Pennsylvania, 15243

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Duke Cancer Center Raleigh

    Raleigh, North Carolina, 27609

  • Queens Cancer Center

    Rego Park, New York, 11374

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Aspirus Cancer Care - James Beck Cancer Center

    Rhinelander, Wisconsin, 54501

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • UT Southwestern Clinical Center at Richardson/Plano

    Richardson, Texas, 75080

  • Reid Health

    Richmond, Indiana, 47374

  • Bon Secours Cancer Institute at Reynolds Crossing

    Richmond, Virginia, 23230

  • VCU Massey Cancer Center at Stony Point

    Richmond, Virginia, 23235

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Kaiser Permanente-Riverside

    Riverside, California, 92505

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Wilmot Cancer Institute Radiation Oncology at Greece

    Rochester, New York, 14606

  • Highland Hospital

    Rochester, New York, 14620

  • University of Rochester

    Rochester, New York, 14642

  • Mercy Cancer Center - Rocklin

    Rocklin, California, 95765

  • Mercy Cancer Center - Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Audie L Murphy VA Hospital

    San Antonio, Texas, 78229

  • Kaiser Permanente-San Diego Zion

    San Diego, California, 92120

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Kaiser Permanente-San Marcos

    San Marcos, California, 92078

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Ridley-Tree Cancer Center

    Santa Barbara, California, 93105

  • UPMC Cancer Center at UPMC Northwest

    Seneca, Pennsylvania, 16346

  • Saint Francis Regional Medical Center

    Shakopee, Minnesota, 55379

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

Other trials in United States

Canada2 sites
  • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)

    Québec, Quebec, G1R 2J6

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

About this study

Official title: Randomized Phase III Trial Incorporating Apalutamide and Advanced Imaging Into Salvage Treatment for Patients With Node-Positive Prostate Cancer After Radical Prostatectomy (INNOVATE*) *INtensifying Treatment for NOde Positive Prostate Cancer by VArying the Hormonal ThErapy

This phase III trial studies whether adding apalutamide 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. Adding apalutamide 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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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:

  1. 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 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 5-6 or 7-8 weeks beginning within 90 days of randomization 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) on days 1-90 of each cycle. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

Patients in both arms may undergo computed tomography (CT), magnetic resonance imaging (MRI), bone scan, and positron emission tomography (PET) as clinically indicated throughout the study. Patients may also undergo blood sample collection throughout the study.

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

Being tested
Apalutamide, Biospecimen Collection, Bone Scan, Computed Tomography, Hormone Therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApalutamideDrug

    Also called ARN 509, ARN-509, ARN509, Erleada

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Hormone TherapyDrug

    Also called Chemotherapy-Hormones/Steroids, Endocrine Therapy, Hormonal, Hormonal Therapy

    Receive hormone therapy

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo pelvis and prostate bed radiation therapy

Study groups in NCT04134260
Study groupRoleWhat they receive
Arm I (hormone therapy, radiation therapy)Active comparatorPatients 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 5-6 or 7-8 weeks beginning within 90 days of randomization in the absence of disease progression or unacceptable toxicity. Patients in both arms may undergo CT, MRI, bone scan, and PET as clinically indicated throughout the study. Patients may also undergo blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Hormone Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy
Arm II (hormone therapy, radiation therapy, apalutamide)ExperimentalPatients undergo standard of care hormone therapy and radiation therapy as in Arm I. Patients also receive apalutamide PO QD on days 1-90 of each cycle. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients in both arms may undergo CT, MRI, bone scan, and PET as clinically indicated throughout the study. Patients may also undergo blood sample collection throughout the study.
Receives: Drug: Apalutamide; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Hormone Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Metastasis-free survival (MFS)

    Kaplan-Meier curves will be generated and metastasis-free survival compared between the two treatment groups by a logrank test, stratified by prostate specific antigen (PSA) level after prostatectomy (never detectable or rising). Cox regression modeling to assess and adjust for the effects of PSA stratum and other baseline covariates will also be performed. The proportional hazards assumption will be tested using Schoenfeld residuals and graphical methods. Martingale residual plots will be examined to determine the best functional form for incorporating covariates into the model. A competing risks analysis will also be performed with time to distant metastasis or death from prostate cancer as the event of interest and death from other causes as the competing risk. Cumulative incidence curves will be generated along with Fine-Gray's test. Patients alive and metastasis free will be censored as of the time of the last negative examination.

    Measured: From randomization to detection of metastatic disease or death from any cause, assessed up to 7.5 years

Secondary outcomes (7)
  1. Quality of life (QOL) between the two treatment arms

    Quality of life scores will be derived by constructing summary measures across domains from the various quality of life instruments (Expanded Prostate Cancer Index Composite-26, EuroQol (EQ)-5 Dimension (D)-5 Level (L), Brief Pain Inventory, and Patient Reported Outcome Measurement Information System-Fatigue). Calculated health utilities will be derived from the EQ-5D-5L instrument and used to produce a quality-adjusted life year survival estimate post-treatment. The area under the curve provides an estimate of the quality-adjusted, restricted mean survival time and will be compared between the two treatment arms as described in Glasziou et al (1990). QOL scores will be analyzed using mixed effects regression for longitudinal data to compare the profiles over time between the two treatment groups (Gibbons and Hedeker, 2000). The models will include treatment, time, and treatment-by-time interaction terms as fixed effects and subjects as a random effect.

    Measured: Up to 3 years post treatment

  2. Overall survival (OS)

    Will be summarized by Kaplan-Meier curves and compared between treatment groups via logrank tests and Cox regression modeling.

    Measured: From randomization until date of death or censored at last date known alive, assessed up to 7.5 years

  3. Biochemical progression-free survival (bPFS)

    Will be summarized by Kaplan-Meier curves and compared between treatment groups via logrank tests and Cox regression modeling. In addition, competing risks analyses will be performed and cumulative incidence curves generated for bPFS with death from other (i.e., non-prostate cancer) causes treated as a competing event. Patients who die from non-prostate cancer related causes will be censored as of the date of death.

    Measured: From randomization until biochemical recurrence or death from prostate cancer, assessed up to 7.5 years

  4. Time to local-regional progression

    Competing risks analyses will be performed and cumulative incidence curves generated for local-regional progression with death from other (i.e., non-prostate cancer) causes treated as a competing event.

    Measured: Up to 7.5 years

  5. Time to castrate resistance

    Will be summarized by Kaplan-Meier curves and compared between treatment groups via logrank tests and Cox regression modeling. Patients who die prior to resistance will be censored.

    Measured: Up to 7.5 years

  6. Cancer-specific survival

    Will be summarized by Kaplan-Meier curves and compared between treatment groups via logrank tests and Cox regression modeling. In addition, competing risks analyses will be performed and cumulative incidence curves generated for cancer-specific survival with death from other (i.e., non-prostate cancer) causes treated as a competing event. Patients who die from non-prostate cancer related causes will be censored as of the date of death.

    Measured: Up to 7.5 years

  7. Incidence of adverse events

    Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be tabulated by type, level of severity, and attribution for each treatment arm and the rate of events compared between treatment groups using chi-square or Fisher's exact tests.

    Measured: Up to 7.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2019
  2. Study start16 Apr 2020
  3. Primary completion1 Nov 2026 (estimated)
  4. Study completion1 Nov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
586 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04134260
Sponsor's protocol ID
NRG-GU008
Other IDs
NCI-2019-06838, NRG-GU008, NRG-GU008, U10CA180868
Status last verified
Aug 2026
First submitted
18 Oct 2019
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Publications

  • Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy. J Urol. 2024 Apr;211(4):518-525. doi: 10.1097/JU.0000000000003891. Epub 2024 Feb 29.

    PubMed 38421243

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