Radiation Therapy in Treating Patients With Stage II Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00033631
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: February 8, 2017
• Last Update Posted: January 18, 2023
• Sponsor: Radiation Therapy Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Tracking Information

• First Submitted Date: April 9, 2002
• First Posted Date: January 27, 2003
• Results First Submitted Date: December 16, 2016
• Results First Posted Date: February 8, 2017
• Last Update Posted Date: January 18, 2023
• Study Start Date: March 2002
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2016)

Overall Survival [ Time Frame: From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years. ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: July 2, 2021)

• Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition [ Time Frame: 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. ]
  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.
• Disease Specific Survival [ Time Frame: 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. ]
  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.
• Local Progression [ Time Frame: From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint. ]
  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.
• Distant Metastases [ Time Frame: From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint. ]
  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.
• Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity [ Time Frame: From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint ]
  Rate of acute 2+ grade genitourinary(GU)/gastrointestinal(GI) toxicity graded by Common Toxicity Criteria (CTC) version 2.0
• Percentage of Participants With Erectile Disfuction at 12 Months [ Time Frame: Twelve months from randomization ]
  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.
• Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months [ Time Frame: Baseline and 12 months from randomization ]
  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.
• Quality Adjusted Survival by SQLI [ Time Frame: From randomization to 5 years. ]
• Tumor Control Probability [ Time Frame: 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 [ Time Frame: From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis. ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• 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
• 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

Study Arms

• Active Comparator: 70.2 Gy
  70.2 Gy 3D-CRT/IMRT
  Intervention: Radiation: 70.2 Gy 3D-CRT/IMRT
• Experimental: 79.2 Gy
  79.2 Gy 3D-CRT/IMRT
  Intervention: Radiation: 79.2 Gy 3D-CRT/IMRT

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 27, 2022): 1534
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 22, 2022
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00033631
• Other Study ID Numbers: RTOG-0126; CDR0000069306
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Radiation Therapy Oncology Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: Radiation Therapy Oncology Group
• Original Study Sponsor: Same as current
• 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

• PRS Account: Radiation Therapy Oncology Group
• Verification Date: December 2022