Clinical trial NCT00033631: Radiation Therapy in Treating Patients With Stage II Prostate Cancer
Official title: A Phase III Randomized Study Of High Dose 3D-CRT/IMRT Versus Standard Dose 3D-CRT/IMRT In Patients Treated For Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 1534
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: RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which dose of radiation therapy is more effective in treating stage II prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different doses of specialized radiation therapy in treating patients who have stage II prostate cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with stage II adenocarcinoma of the prostate treated with high- vs standard-dose three-dimensional conformal or intensity-modulated radiotherapy.
* Compare the freedom from prostate-specific antigen failure, disease-specific survival, local progression, and distant metastases in patients treated with these regimens.
* Compare the probability of tumor control and normal tissue complications in patients treated with these regimens.
* Compare the incidence of grade 2 or greater genitourinary and gastrointestinal acute and late toxicity in patients treated with these regimens.
* Compare the quality of life, including sexual function, of patients treated with these regimens.
* Correlate histopathologic or tumor-specific cytogenetic or chromosomal markers with cancer control outcomes in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Gleason score and prostate-specific antigen (PSA) level (Gleason score 2-6, PSA ≥10 mg/mL but \< 20 ng/mL vs Gleason score 7, PSA \< 15 ng/mL) and radiation modality (three-dimensional conformal radiotherapy \[3D-CRT\] vs intensity-modulated radiotherapy \[IMRT\]). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo standard-dose 3D-CRT or IMRT once daily, 5 days a week, for 7.8 weeks (39 treatment days).
* Arm II: Patients undergo high-dose 3D-CRT or IMRT once daily, 5 days a week, for 8.8 weeks (44 treatment days).

Quality of life (QOL) is assessed initially at baseline. After completion of radiotherapy, QOL is assessed every 3 months for 1 year and then every 6 months for 4 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,520 patients (760 per treatment arm) will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the prostate

  * Clinical stage T1b-T2b
* Meets one of the following criteria:

  * Gleason score 2-6 AND prostate-specific antigen (PSA) ≥ 10 ng/mL but \< 20 ng/mL
  * Gleason score 7 AND PSA \< 15 ng/mL
* No regional lymph node involvement
* No distant metastases

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* No other invasive malignancy within the past 5 years except localized basal cell or squamous cell skin cancer
* No other major medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior cytotoxic chemotherapy
* No concurrent cytotoxic chemotherapy

Endocrine therapy:

* At least 3 months since prior finasteride
* No other prior hormonal therapy, including:

  * Luteinizing hormone-releasing hormone agonists (e.g., goserelin or leuprolide)
  * Antiandrogens (e.g., flutamide or bicalutamide)
  * Estrogens (e.g., diethylstilbestrol)
* No concurrent (neoadjuvant or adjuvant) hormonal therapy

Radiotherapy:

* No prior pelvic irradiation or brachytherapy

Surgery:

* No prior radical surgery (prostatectomy) or cryosurgery for prostate cancer
* No prior surgical castration (bilateral orchiectomy)

Other:

* At least 3 months since prior finasteride or phytoestrogen preparation (PC-SPES)

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years.
Secondary outcomes:
measure: Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition
timeFrame: From randomization to date of failure (3 consecutive rises) or death or last follow-up. Analysis occurred after patients have been potentially followed for 5 years.
measure: Disease Specific Survival
timeFrame: From randomization to date of failure (death due to prostate cancer) or death from other cause or last follow-up. Analysis occurs at the same time as the primary endpoint.
measure: Local Progression
timeFrame: From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.
measure: Distant Metastases
timeFrame: From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.
measure: Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity
timeFrame: From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint
measure: Percentage of Participants With Erectile Disfuction at 12 Months
timeFrame: Twelve months from randomization
measure: Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months
timeFrame: Baseline and 12 months from randomization
measure: Quality Adjusted Survival by SQLI
timeFrame: From randomization to 5 years.
measure: Tumor Control Probability
timeFrame: From randomization to date of failure (tumor progression) or last follow-up. Analysis can occur any time after the primary endpoint analysis.
measure: Normal Tissue Complication Probability
timeFrame: From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis.
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Veterans Affairs Medical Center - Long Beach
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Washington Cancer Institute at Washington Hospital Center
state: District of Columbia
city: Panama City
country: United States
facility: Bay Medical
state: Florida
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Hammond
country: United States
facility: Oncology Center at Saint Margaret Mercy Healthcare Center
state: Indiana
city: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Johnson County Radiation Therapy
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Oncology Center
state: Maryland
city: Ann Arbor
country: United States
facility: Veterans Affairs Medical Center - Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Breslin Cancer Center at Ingham Regional Medical Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Independence
country: United States
facility: Independence Regional Health Center
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center - Hospital Hill
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute at Saint Luke's Hospital
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Center at St. Joseph's Medical Mall
state: Missouri
city: Kansas City
country: United States
facility: St. Joseph Medical Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Parvin Radiation Oncology
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Reno
country: United States
facility: Saint Mary's Regional Medical Center
state: Nevada
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Medical Center - Downtown
state: New Mexico
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina - Raleigh
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center at Rex Hospital
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: West Chester
country: United States
facility: Precision Radiotherapy at University Pointe
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: MNAP Oncologic Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland Air Force Base
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center - Portsmouth
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at Wheaton Franciscan Healthcare
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: Doctor H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Cancer Care Program at Thunder Bay Regional Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Edmond Odette Cancer Centre at Sunnybrook
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Washington University - Saint Louis
name: Jeff M. Michalski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UC Davis
name: James Purdy, Ph.D.
role: STUDY_CHAIR
affiliation: Emory University
name: Deborah W Bruner, Ph.D.
role: STUDY_CHAIR
affiliation: Cedars-Sinai
name: Mahul Amin, M.D.
role: STUDY_CHAIR
References:
citation: Cranmer-Sargison G. A treatment planning investigation into the dosimetric effects of systematic prostate patient rotational set-up errors. Med Dosim. 2008 Autumn;33(3):199-205. doi: 10.1016/j.meddos.2007.06.005.
citation: Potrebko PS, McCurdy BM, Butler JB, El-Gubtan AS, Nugent Z. Optimal starting gantry angles using equiangular-spaced beams with intensity modulated radiation therapy for prostate cancer on RTOG 0126: a clinical study of 5 and 7 fields. Radiother Oncol. 2007 Nov;85(2):299-305. doi: 10.1016/j.radonc.2007.06.019. Epub 2007 Sep 7.
citation: Michalski JM, Moughan J, Purdy J, Bosch W, Bruner DW, Bahary JP, Lau H, Duclos M, Parliament M, Morton G, Hamstra D, Seider M, Lock MI, Patel M, Gay H, Vigneault E, Winter K, Sandler H. Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol. 2018 Jun 14;4(6):e180039. doi: 10.1001/jamaoncol.2018.0039. Epub 2018 Jun 14.