Radiation Therapy in Treating Patients With Prostate Cancer

• ClinicalTrials.gov Identifier: NCT01434290
• Recruitment Status: Completed
• First Posted: September 14, 2011
• Results First Posted: November 17, 2017
• Last Update Posted: June 9, 2022
• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Tracking Information

• First Submitted Date: September 13, 2011
• First Posted Date: September 14, 2011
• Results First Submitted Date: August 24, 2017
• Results First Posted Date: November 17, 2017
• Last Update Posted Date: June 9, 2022
• Study Start Date: September 2011
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 16, 2017)

• Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The co-primary endpoint is the percentage of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) bowel domain score from baseline to 1 year that exceeds 5 points (baseline - one year > 5). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
• The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The co-primary endpoint is the proportion of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) urinary domain score from baseline to 1 year that exceeds 2 points (baseline - one year > 2). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Original Primary Outcome Measures (submitted: September 13, 2011)

• The proportion of patients with change from baseline to the 1-year EPIC bowel-domain score that exceeds 5 points
• The proportion of patients change from baseline to 1 year EPIC urinary-domain score that exceeds 2 points

Current Secondary Outcome Measures (submitted: May 26, 2021)

• Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm [ Time Frame: Start of protocol treatment to one year from the end of protocol treatment ]
  Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of radiation therapy (RT). The high dose RT arm of Radiation Therapy Oncology Group (RTOG) study RTOG-0126 (NCT00033631) reported 1% of patients experienced grade 3+ GI/GU acute toxicity with no patient experiencing a grade 4 or 5 toxicity. If the lower confidence interval is >1%, then that arm will be further investigated for acceptability. A late adverse event is defined as the first occurrence of worst severity of adverse event >30 days after RT completion. Arms are not compared to each other.
• Rate of PSA Failure [ Time Frame: Registration to five years ]
  Failure occurs when the PSA is first noted to be 2 ng/mL or more than the current nadir value (PSA > current nadir + 2) post RT completion. Time to PSA failure is defined as time from registration to the date of PSA failure, last known follow-up (censored), or death without PSA failure (competing risk). Rate of PSA failure is estimated by the cumulative incidence method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.
• Rate of Disease-free Survival (DFS) [ Time Frame: Registration to 5 years ]
  Disease-free survival duration is time from the date of randomization to the date of documentation of disease progression or until the date of death from any cause (censored). DFS is estimated by the Kaplan-Meier method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.
• Mean Quality Adjusted Life Years at 5 Years [ Time Frame: Registration to 5 years from the end of protocol treatment ]
  Quality-adjusted survival time combines disease-free survival time and quality of life as measured by the EuroQol 5-dimensional (EQ-5D) index score. It is calculated for each patient as the weighted sum of different time episodes and added up to total quality-adjusted life years . The EQ-5D measures health-related quality of life and consists of two parts, a general health visual analog scale and 5 general health questions. The latter questions are transformed into a single index score ranging from 0 (worst health state) to 1 (best health state). Arms are not compared to each other.
• Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life and a positive change from baseline indicating improvement over time. For this endpoint, in each domain, the actual change score calculated as timepoint score - baseline score will be used as the statistic.
• The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points [ Time Frame: Baseline one year from the end of protocol treatment ]
  The percentage of patients with a reduction in the EPIC sexual domain score from baseline that exceeds 11 points (baseline - one year > 11). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
• The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The percentage of patients with a reduction in the EPIC hormonal domain score from baseline that exceeds 3 points (baseline - one year > 3). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.
• Change From Baseline in EQ-5D Scores [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score. One, 2, and 5 years will be entered when they are available. Arms are not compared.
• Utilization of Sexual Medications/Devices Questionnaire Response Frequences [ Time Frame: Baseline and one year from the end of protocol treatment ]
  The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The number of subjects responding "Yes" to the following questions are reported: "Do you have a penile prosthesis", "Have you used an medications or devices to aid or improve erections?". Arms are not compared to each other. One, 2, and 5 years will be entered when they are available.
• Genetic Markers Associated With Normal Tissue Toxicities Resulting From Radiotherapy [ Time Frame: Study entry to 5 years from the end of protocol treatment ]

Original Secondary Outcome Measures (submitted: September 13, 2011)

• Acute and late GI and GU toxicity for each arm at 1, 2, and 5 years
• PSA failure at 1, 2, and 5 years
• Disease-free survival at 1, 2, and 5 years
• Quality Adjusted Life Years at 1, 2, and 5 years using the EQ-5D and DFS
• Genetic markers associated with normal tissue toxicities resulting from radiotherapy
• Estimation of EPIC bowel and urinary HRQOL as continuous variables

• 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 Prostate Cancer
• Official Title: A Randomized Phase II Trial of Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Given radiation therapy in different ways may kill more tumor cells.

PURPOSE: This randomized phase II trial studies radiation therapy to see how well it works in treating patients with prostate cancer.

Detailed Description

OBJECTIVES:

Primary

• To demonstrate that 1-year health-related quality of life (HRQOL) for at least one hypofractionated arm is not significantly lower than baseline as measured by the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument.

Secondary

• To estimate the degree of change in HRQOL in each arm for the Sexual and Hormonal EPIC domains and the Utilization of Sexual Medications/Devices from baseline to 1 year, 2 years, and 5 years.
• To estimate the degree of change in global HRQOL in each arm as measured by the Euro Quality of Life, 5 dimensions (EQ-5D) from baseline to 1 year, 2 years, and 5 years.
• To estimate the rate of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity for each arm at 1, 2, and 5 years.
• To estimate prostate-specific antigen (PSA) failure in each arm at 1, 2, and 5 years.
• To estimate disease-free survival (DFS) in each arm at 1, 2, and 5 years.
• To estimate Quality Adjusted Life Years for each arm at 1, 2, and 5 years using the EQ-5D and DFS.
• To identify genetic markers associated with normal tissue toxicities resulting from radiotherapy.
• To collect tumor tissue for biomarker studies.
• To estimate EPIC bowel and urinary HRQOL as continuous variables.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment techniques/machine (all linear accelerator-based treatment [excluding cyberknife] vs cyberknife vs protons). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo hypofractionated radiotherapy using intensity-modulated radiation therapy (IMRT), cyberknife, or protons twice a week for approximately 2½ weeks (36.25 Gy total).
• Arm II: Patients undergo hypofractionated radiotherapy using IMRT, cyberknife, or protons once a day, 5 days a week, for approximately 2½ weeks (51.6 Gy total).

Patients may undergo blood and tumor tissue collection for correlative studies.

Patients may also complete the Utilization of Sexual Medications/Devices, the European Questionnaire-5D, and the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and at 1, 2, and 5 years after completion of radiation therapy.

After completion of study therapy, patients are followed-up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Prostate Cancer
• Psychosocial Effects of Cancer and Its Treatment
• Radiation Toxicity
• Sexual Dysfunction

Intervention

• Radiation: 36.25 Gy IMRT
  36.25 Gy in 5 fractions of 7.5 Gy twice a week over 15-17 days. A minimum of 72 hours and a maximum of 96 hours will separate each treatment. IMRT or similar techniques that use inverse treatment planning or protons are required.
• Radiation: 51.6 Gy IMRT
  51.6 Gy in 12 fractions of 4.3 Gy 5 days a week over 16-18 days. IMRT or similar techniques that use inverse treatment planning or protons are required.

Study Arms

• Experimental: 5 Fractions
  36.25 Gy IMRT in 5 fractions over two and a half weeks
  Intervention: Radiation: 36.25 Gy IMRT
• Experimental: 12 Fractions
  51.6 Gy IMRT in 12 fractions over two and a half weeks
  Intervention: Radiation: 51.6 Gy IMRT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2017): 255
• Original Estimated Enrollment (submitted: September 13, 2011): 174
• Actual Study Completion Date: May 20, 2022
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days of randomization

  • History/physical examination with digital rectal examination of the prostate within 60 days prior to registration
  • Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material; Gleason scores 2-6 within 180 days of randomization
  • Clinical stage T1-2a (AJCC 7th edition) within 90 days of randomization

  • Prostate-specific antigen (PSA) < 10 ng/mL within 60 days prior to registration;

    • PSA should not be obtained within 10 days after prostate biopsy
• No evidence of distant metastases
• No regional lymph node involvement

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire
• No prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease-free for a minimum of 5 years (for example, carcinoma of the oral cavity is permissible; however, patients with prior history of bladder cancer are not allowed)

• No severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

    • Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

  • Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition

    • HIV testing is not required for entry into this protocol
    • Protocol-specific requirements may also exclude immuno-compromised patients

PRIOR CONCURRENT THERAPY:

• No prior radical surgery (prostatectomy), cryosurgery, or high-intensity focused ultrasonography (HIFU) for prostate cancer
• No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
• No prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin, leuprolide) or LHRH antagonists (e.g., degarelix), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol (DES)), or surgical castration (orchiectomy)

• No finasteride within 30 days prior to registration

  • Prostate-specific antigen (PSA) should not be obtained prior to 30 days after stopping finasteride

• No dutasteride within 90 days prior to registration

  • PSA should not be obtained prior to 90 days after stopping dutasteride
• No prior or concurrent cytotoxic chemotherapy for prostate cancer
• Patients on Coumadin or other blood-thinning agents are eligible for this study
• No concurrent 3D-conformal radiation therapy

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: NCT01434290
• Other Study ID Numbers: RTOG 0938; CDR0000703580; NCI-2011-03629 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) )
• 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: Walter John Curran, Jr, Radiation Therapy Oncology Group
• Current Study Sponsor: Radiation Therapy Oncology Group
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Himu R. Lukka, MD; Margaret and Charles Juravinski Cancer Centre

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