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

NCT03809000 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: RTOG 3506STEEL
• Study Type: interventional
• Target: 188
• Locations: 2 countries
• Sites: 108

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Post-prostatectomy; Enzalutamide; STEEL

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Alive Without Progression (Progression-Free Survival)

  Progression-free survival (PFS) is estimated by the Kaplan-Meier method. PFS time is measured from randomization to the date of first PFS failure (biochemical or clinical failure, initiation of new unplanned anticancer treatment, or death from any cause) or last known follow-up (censored). Analysis was to occur after progression or death was reported for 101 participants. Biochemical failure is defined as first post-RT detectable PSA (PSA ≥ 0.05). Clinical failure is defined as either a local, regional, or distant failure.

  From randomization to first failure or last known follow-up. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.

Secondary Outcomes (16)

• Percentage of Participants With Biochemical Failure

  From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.

• Percentage of Participants With Alternative Biochemical Failure

  From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.

• Percentage of Participants With Hormone-refractory Disease

  From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.

• Percentage of Participants With Distant Metastasis

  From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.

• Percentage of Participants With Prostate Cancer Death

  From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.

Study Arms (2)

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

ACTIVE COMPARATOR

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.

Radiation: Radiation Therapy; Drug: Bicalutamide; Drug: GnRH analog

Salvage Radiation Therapy + Enhanced ADT

EXPERIMENTAL

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.

Radiation: Radiation Therapy; Drug: Enzalutamide; Drug: GnRH analog

Interventions

Radiation Therapy RADIATION

daily fractions

Also known as: RT, Image-Guided Radiation Therapy (IGRT), Radiotherapy

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

Enzalutamide DRUG

tablet

Also known as: Xtandi®

Salvage Radiation Therapy + Enhanced ADT

Bicalutamide DRUG

tablet

Also known as: Casodex®

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

GnRH analog DRUG

Injection

Also known as: Gonadotropin-releasing hormone analog, Lupron®, leuprolide acetate, goserelin acetate, Eligard™, Viadur™, Zoladex®, Trelstar®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RTOG Foundation, Inc.: lead
• Pfizer: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (108)

Arizona Center for Cancer Care - Gilbert

Gilbert, Arizona, 85297, United States

Location

Arizona Center for Cancer Care - Peoria

Peoria, Arizona, 85381, United States

Location

Arizona Center for Cancer Care - Phoenix

Phoenix, Arizona, 85027, United States

Location

Arizona Center for Cancer Care - Scottsdale East

Scottsdale, Arizona, 85251, United States

Location

Arizona Center for Cancer Care - Scottsdale North

Scottsdale, Arizona, 85258, United States

Location

Arizona Center for Cancer Care - Surprise

Surprise, Arizona, 85374, United States

Location

Marin Cancer Care, Inc.

Greenbrae, California, 94904, United States

Location

Marin Health Medical Center

Greenbrae, California, 94904, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

USC Medical Center - Los Angeles County

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Roseville Radiation Oncology Center

Roseville, California, 95661, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Valley View Hospital Cancer Center

Glenwood Springs, Colorado, 81601, United States

Location

University of Florida Health Science Center

Gainesville, Florida, 32608, United States

Location

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

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

Savannah, Georgia, 31405, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Crossroads Cancer Center

Effingham, Illinois, 62401, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Kansas University Cancer Center Overland Park

Overland Park, Kansas, 66210, United States

Location

Kansas University Cancer Center Westwood

Westwood, Kansas, 66205, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

LSU Healthcare Network/Metairie Multi-Specialty Clinic

Metairie, Louisiana, 70006, United States

Location

Coastal Cancer Treatment Center - Bath

Bath, Maine, 04530, United States

Location

Waldo Count General Hospital - Belfast

Belfast, Maine, 04915, United States

Location

Maine Health/SMHC Cancer Care and Blood Disorders-Biddeford

Biddeford, Maine, 04005, United States

Location

Maine Health/Stephens Memorial - Norway

Norway, Maine, 04268, United States

Location

Maine Medical Center - Bramhall S Portland

Portland, Maine, 04102, United States

Location

Penobscot Bay Medical Center - Rockport

Rockport, Maine, 04856, United States

Location

Maine Health CC of York County - Sanford

Sanford, Maine, 04073, United States

Location

Maine Health/SMHCancer Care and Blood Disorders - Sanford

Sanford, Maine, 04073, United States

Location

Maine Medical Cancer Center - Scarborough Campus

Scarborough, Maine, 04074, United States

Location

Maine Medical Partners - South Portland

South Portland, Maine, 04106, United States

Location

McLaren Cancer Institute - Bloomfield

Bloomfield, Michigan, 48302, United States

Location

21st Century Oncology MHP - Clarkston

Clarkston, Michigan, 48346, United States

Location

McLaren Cancer Institute - Clarkston

Clarkston, Michigan, 48346, United States

Location

William Beaumont Hospital - Dearborn

Dearborn, Michigan, 48124, United States

Location

Wayne State/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

21st Century Oncology MHP - Farmington

Farmington Hills, Michigan, 48334, United States

Location

McLaren Cancer Institute - Flint

Flint, Michigan, 48532, United States

Location

Singh and Arora Hematology Oncology PC

Flint, Michigan, 48532, United States

Location

McLaren Cancer Institute - Greater Lansing

Lansing, Michigan, 48910, United States

Location

Mid-Michigan Physicians - Lansing

Lansing, Michigan, 48912, United States

Location

McLaren Cancer Institute - Lapeer Region

Lapeer, Michigan, 48446, United States

Location

21st Century Oncology MHP - Macomb

Macomb, Michigan, 48044, United States

Location

21st Century Oncology MHP - Madison Heights

Madison Heights, Michigan, 48071, United States

Location

McLaren Cancer Institute - Macomb

Mount Clemens, Michigan, 48043, United States

Location

McLaren Cancer Institute - Central Michigan

Mount Pleasant, Michigan, 48858, United States

Location

McLaren Cancer Institute - Owosso

Owosso, Michigan, 48867, United States

Location

McLaren Cancer Institute - Northern Michigan

Petoskey, Michigan, 49770, United States

Location

McLaren Cancer Institute - Port Huron

Port Huron, Michigan, 48060, United States

Location

William Beaumont Hospital - Royal Oak

Royal Oak, Michigan, 48073, United States

Location

William Beaumont Hospital - Troy

Sterling Heights, Michigan, 48314, United States

Location

21st Century Oncology MHP - Troy

Troy, Michigan, 48098, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Minnesota Oncology Hematology PA - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Coborn Cancer Center

Saint Cloud, Minnesota, 56303, United States

Location

HealthPartners, Inc.

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Kansas University Cancer Center North

Kansas City, Missouri, 64154, United States

Location

Kansas University Cancer Center Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Exeter Hospital

Exeter, New Hampshire, 03833, United States

Location

Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

University Physicians at Oneida

Oneida, New York, 13421, United States

Location

Upstate Cancer Center Radiation Oncology at Oneida

Oneida, New York, 13421, United States

Location

University Physicians at Oswego

Oswego, New York, 13126, United States

Location

Upstate Cancer Radiation Oncology at Oswego

Oswego, New York, 13126, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Upstate Cancer Center at Hill Radiation Oncology

Syracuse, New York, 13210, United States

Location

UNC Rex Cancer Center

Raleigh, North Carolina, 27607, United States

Location

Rex Cancer Center of Wakefield

Raleigh, North Carolina, 27614, United States

Location

WellSpan Health - Ephrata Cancer Center

Ephrata, Pennsylvania, 17522, United States

Location

WellSpan Health - Adams Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

WellSpan Health - Sechler Family Cancer Center

Lebanon, Pennsylvania, 17402, United States

Location

University of Pittsburgh Medical Center - Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

WellSpan Health - York Hospital

York, Pennsylvania, 17403, United States

Location

Gibbs Cancer Center - Pelham

Greer, South Carolina, 29650, United States

Location

Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

UT Southwestern/Simmons Cancer Center - Dallas

Dallas, Texas, 75390, United States

Location

American Fork Hospital

American Fork, Utah, 84003, United States

Location

Cedar City Hospital

Cedar City, Utah, 84721, United States

Location

Logan Regional Medical Center

Logan, Utah, 84341, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Utah Valley Regional Medical Center

Provo, Utah, 84604, United States

Location

Dixie Regional Medical Center

St. George, Utah, 84790, United States

Location

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

Saint Johnsbury, Vermont, 05819, United States

Location

Sentara Cancer Institute at Sentara CarePlex Hospital

Hampton, Virginia, 23666, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Sentara Virginia Beach General Hospital

Virginia Beach, Virginia, 23454, United States

Location

Aspirus Langlade Hospital

Antigo, Wisconsin, 54409, United States

Location

University Cancer Center Johnson Creek

Johnson Creek, Wisconsin, 53038, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin, 53051, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Drexel Town Square

Oak Creek, Wisconsin, 53154, United States

Location

Aspirus Regional Cancer Center

Wausau, Wisconsin, 54401, United States

Location

Froedtert West Bend Hospital

West Bend, Wisconsin, 53095, United States

Location

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, 54494, United States

Location

CHU de Quebec - L'Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

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

Sherbrooke, J1H 5N4, Canada

Location

Related Publications (1)

• 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.

  PMID: 38421243 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy; Radiotherapy, Image-Guided; enzalutamide; bicalutamide; Gonadotropin-Releasing Hormone; Leuprolide; Goserelin; luprolide acetate gel depot; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

The sample size calculation was modified due to a change in eligibility, however the sample size itself remained the same at 242 patients since the hazard ratio was reduced of 0.65 to 0.63. Later, a change in the definition of biochemical failure which is a component of the primary endpoint of PFS decreased the sample size to 170 patients.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: American College of Radiology

wseiferheld@acr.org

2155743208

Study Officials

• Edwin Posadas, MD

  RTOG Foundation

  PRINCIPAL INVESTIGATOR

• Hiram Gay, MD

  RTOG Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2019
• First Posted: January 18, 2019
• Study Start: April 15, 2019
• Primary Completion: April 7, 2023
• Study Completion (Estimated): September 15, 2029
• Last Updated: December 30, 2025
• Results First Posted: October 16, 2024

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (106)