Radiation Therapy in Treating Patients With Stage II Prostate Cancer

A Phase III Randomized Study Of High Dose 3D-CRT/IMRT Versus Standard Dose 3D-CRT/IMRT In Patients Treated For Localized Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: 70.2 Gy 3D-CRT/IMRT; Radiation: 79.2 Gy 3D-CRT/IMRT

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.

• Study Type: Interventional
• Enrollment (Actual): 1534
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre - Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Doctor H. Bliss Murphy Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Cancer Care Program at Thunder Bay Regional Health Sciences
    • Toronto, Ontario, Canada, M4N 3M5
      • Edmond Odette Cancer Centre at Sunnybrook
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre-Dame du CHUM
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• United States
  • California
    • Long Beach, California, United States, 90822
      • Veterans Affairs Medical Center - Long Beach
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute at Washington Hospital Center
  • Florida
    • Panama City, Florida, United States, 32401
      • Bay Medical
  • Illinois
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
  • Indiana
    • Hammond, Indiana, United States, 46320
      • Oncology Center at Saint Margaret Mercy Healthcare Center
    • Muncie, Indiana, United States, 47303-3499
      • Cancer Center at Ball Memorial Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • Providence Medical Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66210
      • Johnson County Radiation Therapy
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Oncology Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs Medical Center - Ann Arbor
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Independence, Missouri, United States, 64050
      • Independence Regional Health Center
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center - Hospital Hill
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64114
      • St. Joseph Medical Center
    • Kansas City, Missouri, United States, 64116
      • Parvin Radiation Oncology
    • Kansas City, Missouri, United States, 64114
      • Kansas City Cancer Center at St. Joseph's Medical Mall
    • Kansas City, Missouri, United States, 64154
      • Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Nevada
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at Cooper University Hospital - Camden
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center - Downtown
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Brooklyn, New York, United States, 11209
      • Veterans Affairs Medical Center - Brooklyn
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Rex Cancer Center at Rex Hospital
    • Raleigh, North Carolina, United States, 27607
      • Cancer Centers of North Carolina - Raleigh
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • West Chester, Ohio, United States, 45069
      • Precision Radiotherapy at University Pointe
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Paoli, Pennsylvania, United States, 19301-1792
      • Cancer Center of Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19115
      • MNAP Oncologic Center
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - Main Line Health
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Lackland Air Force Base, Texas, United States, 78236
      • Wilford Hall Medical Center
  • Utah
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center - Portsmouth
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital Cancer Care Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 70.2 Gy; 70.2 Gy 3D-CRT/IMRT	Radiation: 70.2 Gy 3D-CRT/IMRT; Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.; Other Names: 3D conformal radiation therapy; intensity modulated radiation therapy
Experimental: 79.2 Gy; 79.2 Gy 3D-CRT/IMRT	Radiation: 79.2 Gy 3D-CRT/IMRT; Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.; Other Names: 3D conformal radiation therapy; intensity modulated radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier Method. Patients last know to be alive are censored at date of last contact.	From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition	Failure is defined as having 3 consecutive elevations of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before three consecutive elevations were documented. The failure day date was the midpoint between last non-rising PSA and first PSA rise. Failure rates are estimated by the cumulative incidence method. Patients last known to be alive are censored at date of last contact.	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.
Disease Specific Survival	Survival time is defined as time from randomization to the date of death due to prostate cancer and is estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. Death due to prostate cancer was defined as primary cause of death certified as due to prostate cancer, or death in association with any of the following conditions: Further clinical tumor progression occurring after initiation of salvage anti-tumor therapy, a rise (that exceeds 1.0 ng/ml) in the serum PSA level on at least two consecutive occasions that occurred during or after salvage androgen suppression therapy, or disease progression in the absence of any anti-tumor therapy.	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.
Local Progression	Failure time is defined as time from randomization to the date of progression (increase in palpable abnormality), failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.	From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.
Distant Metastases	Failure time is defined as time from randomization to the date of documented regional nodal recurrence or development of distant disease. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.	From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.
Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity	Rate of acute 2+ grade genitourinary(GU)/gastrointestinal(GI) toxicity graded by Common Toxicity Criteria (CTC) version 2.0	From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint
Percentage of Participants With Erectile Disfuction at 12 Months	The International Index of Erectile Function Questionnaire (IIEF) is the primary measure for erectile function (ED). IIEF question number 1 ("How often were you able to get an erection during sexual activity?") is scored from: none/almost never (response 0-1) or < half the time (response 2-3) to most times/almost always/always (response 4-5). A response of 0 to 3 on question number 1 of the IIEF is considered erectile dysfunction.	Twelve months from randomization
Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months	The SQLI measures quality of life for patients with cancer and other chronic diseases. Possible scores range from 0 to 10, with higher scores indicating a better outcome. Change from Baseline is defined as 12 month SQLI - baseline SQLI and is classified as follows: Improvement: when change >= to the standard error of measurement with reliability quotient of 0.5 (SEM); Stable: when -SEM < change < SEM; Declined: when change <= SEM.	Baseline and 12 months from randomization
Quality Adjusted Survival by SQLI		From randomization to 5 years.
Tumor Control Probability		From randomization to date of failure (tumor progression) or last follow-up. Analysis can occur any time after the primary endpoint analysis.
Normal Tissue Complication Probability		From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeff M. Michalski, MD, Washington University - Saint Louis; Study Chair: James Purdy, Ph.D., UC Davis; Study Chair: Deborah W Bruner, Ph.D., Emory University; Study Chair: Mahul Amin, M.D., Cedars-Sinai

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: RTOG-0126; CDR0000069306