Clinical trial NCT03809000: A Study of Salvage Radiotherapy With or Without Enzalutamide in Recurrent Prostate Cancer Following Surgery
Official title: STEEL: A Randomized Phase II Trial of Salvage Radiotherapy With Standard vs Enhanced Androgen Deprivation Therapy (With Enzalutamide) in Patients With Post-Prostatectomy PSA Recurrences With Aggressive Disease Features
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Post-prostatectomy
Enzalutamide
STEEL
Lead sponsor: RTOG Foundation, Inc.
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Astellas Pharma Inc
First posted: 2019-01-18
Enrollment: 188
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (Percentage of Participants Alive Without Progression)
timeFrame: From date of randomization to the date of progression, death from any cause, or last known follow-up, whichever occurs first. Maximum follow-up time was 40.2 months. The 6 and 12 months PFS estimates are reported.
Secondary outcomes:
measure: Biochemical Failure (Percentage of Participants With Biochemical Failure)
timeFrame: From date of randomization to date of failure, death, or last known follow-up, whichever occurs first, at a minimum of two years from start of treatment, and up to six years.
measure: Alternative Biochemical Failure (Percentage of Participants With Alternative Biochemical Failure)
timeFrame: From date of randomization to the date failure, death, or last known follow-up, whichever occurs first, at a minimum of two years from start of treatment, and up to six years.
measure: Hormone-refractory Disease (Percentage of Participants With Hormone-refractory Disease)
timeFrame: From randomization to the date of failure, death, or last known follow-up, whichever occurs first, at a minimum of two years from start of treatment, and up to six years.
measure: Distant Metastasis (Percentage of Participants With Distant Metastasis)
timeFrame: From date of randomization to the date of failure, death, or last known follow-up, whichever occurs first, at a minimum of two years from start of treatment, and up to six years.
measure: Cause-specific Mortality (Percentage of Participants Who Have Not Died Due to Prostate Cancer)
timeFrame: From randomization to the date death or last known follow-up, at a minimum of two years from start of treatment, and up to six years.
measure: Overall Survival (Percentage of Participants Alive)
timeFrame: From date of randomization to the date of death or last known follow-up, at a minimum of two years from start of treatment, and up to six years.
measure: Change From Baseline in 5-level European Quality of Life Questionnaire (EQ-5D-5L)
timeFrame: Baseline, end* of radiation treatment (RT), one year, two years. (*End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks. )
measure: Change From Baseline in the 7 Item Patient Reported Outcomes Measurement Information System Fatigue Short Form (PROMIS-F SF 7a) Score
timeFrame: Baseline, end* of radiation treatment (RT), one year, two years. (*End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks. )
measure: Toxicity as Measured by CTCAE v5
timeFrame: From date of randomization to date of last known follow-up, at a minimum of two years from start of treatment, and up to six years.
measure: Toxicity as Measured by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: From randomization to 2 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Arizona Center for Cancer Care - Gilbert
state: Arizona
city: Peoria
country: United States
facility: Arizona Center for Cancer Care - Peoria
state: Arizona
city: Phoenix
country: United States
facility: Arizona Center for Cancer Care - Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Center for Cancer Care - Scottsdale East
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Center for Cancer Care - Scottsdale North
state: Arizona
city: Surprise
country: United States
facility: Arizona Center for Cancer Care - Surprise
state: Arizona
city: Greenbrae
country: United States
facility: Marin Cancer Care, Inc.
state: California
city: Greenbrae
country: United States
facility: Marin Health Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: USC Medical Center - Los Angeles County
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Roseville
country: United States
facility: Roseville Radiation Oncology Center
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Glenwood Springs
country: United States
facility: Valley View Hospital Cancer Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Savannah
country: United States
facility: Nancy N. & J.C. Lewis Cancer & Research Pavilion
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas University Cancer Center Overland Park
state: Kansas
city: Westwood
country: United States
facility: Kansas University Cancer Center Westwood
state: Kansas
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Metairie
country: United States
facility: LSU Healthcare Network/Metairie Multi-Specialty Clinic
state: Louisiana
city: Bath
country: United States
facility: Coastal Cancer Treatment Center - Bath
state: Maine
city: Belfast
country: United States
facility: Waldo Count General Hospital - Belfast
state: Maine
city: Biddeford
country: United States
facility: Maine Health/SMHC Cancer Care and Blood Disorders-Biddeford
state: Maine
city: Norway
country: United States
facility: Maine Health/Stephens Memorial - Norway
state: Maine
city: Portland
country: United States
facility: Maine Medical Center - Bramhall S Portland
state: Maine
city: Rockport
country: United States
facility: Penobscot Bay Medical Center - Rockport
state: Maine
city: Sanford
country: United States
facility: Maine Health CC of York County - Sanford
state: Maine
city: Sanford
country: United States
facility: Maine Health/SMHCancer Care and Blood Disorders - Sanford
state: Maine
city: Scarborough
country: United States
facility: Maine Medical Cancer Center - Scarborough Campus
state: Maine
city: South Portland
country: United States
facility: Maine Medical Partners - South Portland
state: Maine
city: Bloomfield
country: United States
facility: McLaren Cancer Institute - Bloomfield
state: Michigan
city: Clarkston
country: United States
facility: 21st Century Oncology MHP - Clarkston
state: Michigan
city: Clarkston
country: United States
facility: McLaren Cancer Institute - Clarkston
state: Michigan
city: Dearborn
country: United States
facility: William Beaumont Hospital - Dearborn
state: Michigan
city: Detroit
country: United States
facility: Wayne State/Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: 21st Century Oncology MHP - Farmington
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute - Flint
state: Michigan
city: Flint
country: United States
facility: Singh and Arora Hematology Oncology PC
state: Michigan
city: Lansing
country: United States
facility: McLaren Cancer Institute - Greater Lansing
state: Michigan
city: Lansing
country: United States
facility: Mid-Michigan Physicians - Lansing
state: Michigan
city: Lapeer
country: United States
facility: McLaren Cancer Institute - Lapeer Region
state: Michigan
city: Macomb
country: United States
facility: 21st Century Oncology MHP - Macomb
state: Michigan
city: Madison Heights
country: United States
facility: 21st Century Oncology MHP - Madison Heights
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Cancer Institute - Macomb
state: Michigan
city: Mount Pleasant
country: United States
facility: McLaren Cancer Institute - Central Michigan
state: Michigan
city: Owosso
country: United States
facility: McLaren Cancer Institute - Owosso
state: Michigan
city: Petoskey
country: United States
facility: McLaren Cancer Institute - Northern Michigan
state: Michigan
city: Port Huron
country: United States
facility: McLaren Cancer Institute - Port Huron
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak
state: Michigan
city: Sterling Heights
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Troy
country: United States
facility: 21st Century Oncology MHP - Troy
state: Michigan
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA - Maplewood
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: HealthPartners, Inc.
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Kansas University Cancer Center North
state: Missouri
city: Lee's Summit
country: United States
facility: Kansas University Cancer Center Lee's Summit
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Exeter
country: United States
facility: Exeter Hospital
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center
state: New Hampshire
city: Oneida
country: United States
facility: University Physicians at Oneida
state: New York
city: Oneida
country: United States
facility: Upstate Cancer Center Radiation Oncology at Oneida
state: New York
city: Oswego
country: United States
facility: University Physicians at Oswego
state: New York
city: Oswego
country: United States
facility: Upstate Cancer Radiation Oncology at Oswego
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Upstate Cancer Center at Hill Radiation Oncology
state: New York
city: Raleigh
country: United States
facility: UNC Rex Cancer Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center of Wakefield
state: North Carolina
city: Ephrata
country: United States
facility: WellSpan Health - Ephrata Cancer Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: WellSpan Health - Adams Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Lebanon
country: United States
facility: WellSpan Health - Sechler Family Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Shadyside Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health - York Hospital
state: Pennsylvania
city: Greer
country: United States
facility: Gibbs Cancer Center - Pelham
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center - Dallas
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Cedar City Hospital
state: Utah
city: Logan
country: United States
facility: Logan Regional Medical Center
state: Utah
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: Saint Johnsbury
country: United States
facility: Dartmouth Hitchcock Medical Center/Norris Cancer Ctr. - St. Johnsbury
state: Vermont
city: Hampton
country: United States
facility: Sentara Cancer Institute at Sentara CarePlex Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Virginia Beach General Hospital
state: Virginia
city: Antigo
country: United States
facility: Aspirus Langlade Hospital
state: Wisconsin
city: Johnson Creek
country: United States
facility: University Cancer Center Johnson Creek
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Froedtert Menomonee Falls Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
city: Oak Creek
country: United States
facility: Drexel Town Square
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: West Bend
country: United States
facility: Froedtert West Bend Hospital
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
city: Québec City
country: Canada
facility: CHU de Quebec - L'Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSS de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Study officials:
affiliation: RTOG Foundation
name: Edwin Posadas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTOG Foundation
name: Hiram Gay, MD
role: PRINCIPAL_INVESTIGATOR
References: