A Study of Salvage Radiotherapy With or Without Enzalutamide in Recurrent Prostate Cancer Following Surgery

NCT ID: NCT03809000

Last Updated: 2025-12-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

188 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-15

Study Completion Date

2029-09-15

Brief Summary

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Patients with post-prostatectomy PSA (Prostate Specific Antigen) recurrences with aggressive disease features will receive salvage radiation therapy and standard androgen deprivation therapy (ADT) or enhanced ADT to determine if there is any improvement in progression-free survival when enhanced ADT is used compared to standard ADT.

Detailed Description

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PRIMARY OBJECTIVE:

To determine whether, in men with post-prostatectomy PSA (prostate specific antigen) recurrences with aggressive disease features, salvage radiotherapy (SRT) with enhanced androgen deprivation therapy (ADT), consisting of enzalutamide (MDV3100) and a GnRH analog, will improve progression-free survival compared to SRT with standard GnRH analog -based ADT.

Conditions

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Prostate Cancer

Keywords

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Post-prostatectomy Enzalutamide STEEL

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT)

Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day).

SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.

Group Type ACTIVE_COMPARATOR

Radiation Therapy

Intervention Type RADIATION

daily fractions

Bicalutamide

Intervention Type DRUG

tablet

GnRH analog

Intervention Type DRUG

Injection

Salvage Radiation Therapy + Enhanced ADT

Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day).

SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.

Group Type EXPERIMENTAL

Radiation Therapy

Intervention Type RADIATION

daily fractions

Enzalutamide

Intervention Type DRUG

tablet

GnRH analog

Intervention Type DRUG

Injection

Interventions

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Radiation Therapy

daily fractions

Intervention Type RADIATION

Enzalutamide

tablet

Intervention Type DRUG

Bicalutamide

tablet

Intervention Type DRUG

GnRH analog

Injection

Intervention Type DRUG

Other Intervention Names

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RT Image-Guided Radiation Therapy (IGRT) Radiotherapy Xtandi® Casodex® Gonadotropin-releasing hormone analog Lupron® leuprolide acetate goserelin acetate Eligard™ Viadur™ Zoladex® Trelstar®

Eligibility Criteria

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Inclusion Criteria

* Pathologically (histologically) proven adenocarcinoma confirmed by prostatectomy performed within 10 years prior to registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted.
* Prostate-specific antigen (PSA) level (≥ 0.2 ng/mL) within 120 days prior to registration. Patients must have a PSA ≥ 0.2 ng/mL prior to starting ADT. For patients being followed by an ultrasensitive PSA assay, a serum PSA concentration of ≥ 0.10 ng/mL will be considered eligible.
* GnRH analog may be started no more than 42 days prior study entry.
* Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to registration.
* Platelet count ≥ 75,000 x 10\^9/µL independent of transfusion and/or growth factors within 90 days prior to registration.
* At least 1 of the following aggressive features:

* Gleason score of 8-10 (note any Gleason score is eligible)
* Seminal vesicle invasion (SVI) (note any pT stage American Joint Committee on Cancer (AJCC) v8.0 is eligible but a pT stage

≥ pT3b is considered aggressive)
* Locoregional node involvement at radical prostatectomy (RP) (pN1)
* Persistently elevated PSA post-RP nadir (PEPP) defined as PSA \> 0.1 ng/mL after radical prostatectomy
* PSA ≥ 0.7 ng/mL
* Serum albumin ≥ 3.0 g/dL within 90 days prior to 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 registration.
* Serum total bilirubin ≤1.5 × upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject is eligible) within 90 days prior to registration.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5 × ULN within 90 days prior to registration.
* History and physical with Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 or within 90 days prior to registration.

Exclusion Criteria

* Definitive clinical or radiologic evidence of metastatic disease with the exception of locoregional lymph nodes.
* 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: 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:

* Documented inflammatory bowel disease
* Transmural myocardial infarction within the last 4 months prior to registration.
* New York Heart Association Functional Classification III/IV within 4 months prior to registration.
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 4 months prior to registration
* History of loss of consciousness or transient ischemic attack within 12 months prior to randomization
* History of seizure disorder or condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
* History of uncontrolled hypertension defined as a sustained systolic blood pressure in excess of 150 mmHg or a sustained diastolic blood pressure in excess of 90 mmHg despite optimized antihypertensive therapy.
* History of repeated falls and fractures over the past 12 months that in the opinion of the treating investigator would put the patient at risk for poor bone outcomes from androgen receptor targeted therapy
* Known gastrointestinal disorder affecting absorption of oral medications.
* Active uncontrolled infection defined as an identified infectious condition that requires active therapy that has not yet been completed.
* HIV positive patients with CD4 count \< 200 cells/microliter within 30 days prior to registration OR 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. This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive and/or interact with HAART.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role collaborator

RTOG Foundation, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edwin Posadas, MD

Role: PRINCIPAL_INVESTIGATOR

RTOG Foundation

Hiram Gay, MD

Role: PRINCIPAL_INVESTIGATOR

RTOG Foundation

Locations

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Arizona Center for Cancer Care - Gilbert

Gilbert, Arizona, United States

Site Status

Arizona Center for Cancer Care - Peoria

Peoria, Arizona, United States

Site Status

Arizona Center for Cancer Care - Phoenix

Phoenix, Arizona, United States

Site Status

Arizona Center for Cancer Care - Scottsdale East

Scottsdale, Arizona, United States

Site Status

Arizona Center for Cancer Care - Scottsdale North

Scottsdale, Arizona, United States

Site Status

Arizona Center for Cancer Care - Surprise

Surprise, Arizona, United States

Site Status

Marin Cancer Care, Inc.

Greenbrae, California, United States

Site Status

Marin Health Medical Center

Greenbrae, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

USC Medical Center - Los Angeles County

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Roseville Radiation Oncology Center

Roseville, California, United States

Site Status

Sutter Roseville Medical Center

Roseville, California, United States

Site Status

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Valley View Hospital Cancer Center

Glenwood Springs, Colorado, United States

Site Status

University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Nancy N. & J.C. Lewis Cancer & Research Pavilion

Savannah, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

Kansas University Cancer Center Overland Park

Overland Park, Kansas, United States

Site Status

Kansas University Cancer Center Westwood

Westwood, Kansas, United States

Site Status

East Jefferson General Hospital

Metairie, Louisiana, United States

Site Status

LSU Healthcare Network/Metairie Multi-Specialty Clinic

Metairie, Louisiana, United States

Site Status

Coastal Cancer Treatment Center - Bath

Bath, Maine, United States

Site Status

Waldo Count General Hospital - Belfast

Belfast, Maine, United States

Site Status

Maine Health/SMHC Cancer Care and Blood Disorders-Biddeford

Biddeford, Maine, United States

Site Status

Maine Health/Stephens Memorial - Norway

Norway, Maine, United States

Site Status

Maine Medical Center - Bramhall S Portland

Portland, Maine, United States

Site Status

Penobscot Bay Medical Center - Rockport

Rockport, Maine, United States

Site Status

Maine Health CC of York County - Sanford

Sanford, Maine, United States

Site Status

Maine Health/SMHCancer Care and Blood Disorders - Sanford

Sanford, Maine, United States

Site Status

Maine Medical Cancer Center - Scarborough Campus

Scarborough, Maine, United States

Site Status

Maine Medical Partners - South Portland

South Portland, Maine, United States

Site Status

McLaren Cancer Institute - Bloomfield

Bloomfield, Michigan, United States

Site Status

21st Century Oncology MHP - Clarkston

Clarkston, Michigan, United States

Site Status

McLaren Cancer Institute - Clarkston

Clarkston, Michigan, United States

Site Status

William Beaumont Hospital - Dearborn

Dearborn, Michigan, United States

Site Status

Wayne State/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

21st Century Oncology MHP - Farmington

Farmington Hills, Michigan, United States

Site Status

McLaren Cancer Institute - Flint

Flint, Michigan, United States

Site Status

Singh and Arora Hematology Oncology PC

Flint, Michigan, United States

Site Status

McLaren Cancer Institute - Greater Lansing

Lansing, Michigan, United States

Site Status

Mid-Michigan Physicians - Lansing

Lansing, Michigan, United States

Site Status

McLaren Cancer Institute - Lapeer Region

Lapeer, Michigan, United States

Site Status

21st Century Oncology MHP - Macomb

Macomb, Michigan, United States

Site Status

21st Century Oncology MHP - Madison Heights

Madison Heights, Michigan, United States

Site Status

McLaren Cancer Institute - Macomb

Mount Clemens, Michigan, United States

Site Status

McLaren Cancer Institute - Central Michigan

Mount Pleasant, Michigan, United States

Site Status

McLaren Cancer Institute - Owosso

Owosso, Michigan, United States

Site Status

McLaren Cancer Institute - Northern Michigan

Petoskey, Michigan, United States

Site Status

McLaren Cancer Institute - Port Huron

Port Huron, Michigan, United States

Site Status

William Beaumont Hospital - Royal Oak

Royal Oak, Michigan, United States

Site Status

William Beaumont Hospital - Troy

Sterling Heights, Michigan, United States

Site Status

21st Century Oncology MHP - Troy

Troy, Michigan, United States

Site Status

Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Minnesota Oncology Hematology PA - Maplewood

Maplewood, Minnesota, United States

Site Status

Coborn Cancer Center

Saint Cloud, Minnesota, United States

Site Status

HealthPartners, Inc.

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

Kansas University Cancer Center North

Kansas City, Missouri, United States

Site Status

Kansas University Cancer Center Lee's Summit

Lee's Summit, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Exeter Hospital

Exeter, New Hampshire, United States

Site Status

Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

University Physicians at Oneida

Oneida, New York, United States

Site Status

Upstate Cancer Center Radiation Oncology at Oneida

Oneida, New York, United States

Site Status

University Physicians at Oswego

Oswego, New York, United States

Site Status

Upstate Cancer Radiation Oncology at Oswego

Oswego, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Upstate Cancer Center at Hill Radiation Oncology

Syracuse, New York, United States

Site Status

UNC Rex Cancer Center

Raleigh, North Carolina, United States

Site Status

Rex Cancer Center of Wakefield

Raleigh, North Carolina, United States

Site Status

WellSpan Health - Ephrata Cancer Center

Ephrata, Pennsylvania, United States

Site Status

WellSpan Health - Adams Cancer Center

Gettysburg, Pennsylvania, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

WellSpan Health - Sechler Family Cancer Center

Lebanon, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center - Shadyside Hospital

Pittsburgh, Pennsylvania, United States

Site Status

WellSpan Health - York Hospital

York, Pennsylvania, United States

Site Status

Gibbs Cancer Center - Pelham

Greer, South Carolina, United States

Site Status

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status

UT Southwestern/Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

American Fork Hospital

American Fork, Utah, United States

Site Status

Cedar City Hospital

Cedar City, Utah, United States

Site Status

Logan Regional Medical Center

Logan, Utah, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Utah Valley Regional Medical Center

Provo, Utah, United States

Site Status

Dixie Regional Medical Center

St. George, Utah, United States

Site Status

Dartmouth Hitchcock Medical Center/Norris Cancer Ctr. - St. Johnsbury

Saint Johnsbury, Vermont, United States

Site Status

Sentara Cancer Institute at Sentara CarePlex Hospital

Hampton, Virginia, United States

Site Status

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Site Status

Sentara Virginia Beach General Hospital

Virginia Beach, Virginia, United States

Site Status

Aspirus Langlade Hospital

Antigo, Wisconsin, United States

Site Status

University Cancer Center Johnson Creek

Johnson Creek, Wisconsin, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, United States

Site Status

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Drexel Town Square

Oak Creek, Wisconsin, United States

Site Status

Aspirus Regional Cancer Center

Wausau, Wisconsin, United States

Site Status

Froedtert West Bend Hospital

West Bend, Wisconsin, United States

Site Status

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, United States

Site Status

CHU de Quebec - L'Hotel-Dieu de Quebec

Québec, Quebec, Canada

Site Status

CIUSS de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, , Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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STEEL

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG 3506

Identifier Type: -

Identifier Source: org_study_id