Clinical Trials /

Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

NCT03570827

Description:

This phase II trial studies how well hypofractionated radiation therapy works in treating participants with prostate cancer high-risk features following radical prostatectomy. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy
  • Official Title: A Phase II Trial of Hypofractionated Radiation Therapy for Prostate Cancer With High Risk Features After Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: MC1754
  • SECONDARY ID: NCI-2018-00943
  • SECONDARY ID: MC1754
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03570827

Conditions

  • Prostate Adenocarcinoma
  • PSA Level Less Than Two
  • Stage IIB Prostate Cancer AJCC v8
  • Stage III Prostate Cancer AJCC v8
  • Stage IIIA Prostate Cancer AJCC v8
  • Stage IIIB Prostate Cancer AJCC v8
  • Stage IIIC Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Androgen Suppressionandrogen ablation, androgen deprivationGroup II (radiation therapy, androgen suppression therapy)

Purpose

This phase II trial studies how well hypofractionated radiation therapy works in treating participants with prostate cancer high-risk features following radical prostatectomy. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine if stereotactic body radiation therapy (SBRT) would result in similar freedom
      from failure (FFF) than standard fractionation photon therapy.

      SECONDARY OBJECTIVES:

      I. After completion of radiation therapy, determine the incidence of grade 2 or greater
      genitourinary (GU) and gastrointestinal (GI) toxicity at 6 months (Common Terminology
      Criteria for Adverse Events [CTCAE] version 4).

      II. After completion of radiation therapy, determine the incidence of grade 3 or greater GU
      and GI toxicity at 6 months (CTCAE version 4).

      III. After completion of radiation therapy, determine the incidence of quality of life issues
      following completion of radiation therapy.

      IV. After completion of radiation therapy, determine the incidence of impotence after the use
      of radiation therapy at 3 years.

      V. After completion of radiation therapy, determine the incidence of freedom from biochemical
      failure (FFBF) at 5 years.

      VI. After completion of radiation therapy, determine the incidence of clinical failure: local
      and/or distant at 5 years.

      VII. After completion of radiation therapy, determine the incidence of salvage androgen
      deprivation use (SAD) at 5 years.

      VIII. After completion of radiation therapy, determine the incidence of progression free
      survival: using clinical, biochemical and SAD as events at 5 years.

      IX. After completion of radiation therapy, determine the incidence of overall survival at 5
      years.

      X. After completion of radiation therapy, determine the incidence of disease-specific
      survival at 5 years.

      XI. Determine the impact of radiation therapy on quality of life. XII. Determine overall GI
      and GU toxicity. XIII. Determine prostate and normal structure movement during radiation
      therapy (RT) with the use of scans.

      XIV. Correlate pathologic and radiologic findings with outcomes. XV. Correlate pre-RT
      prostate specific antigen (PSA) levels with outcomes. XVI. Correlate variation in proton
      therapy or x-ray dosimetry and outcomes. XVII. Develop a quality assurance process for
      prostate proton therapy. XVIII. Prospectively collect information that will help to define
      dose-volume relationships of normal structures with acute and chronic toxicity.

      XIX. Allow for future research of pathologic risk factors that may influence prognosis; this
      information will help us to attempt to characterize their presence in prostate cancer with
      high risk features after prostatectomy and their potential effect on outcomes.

      XX. Possibly compare dosimetric parameters of an IMRT plan with the proton therapy radiation
      plan.

      OUTLINE: Participants are assigned to 1 of 3 groups.

      GROUP I: Participants undergo hypofractionated radiation therapy over 15-30 minutes every
      other day over 2 weeks, for 5 treatments.

      GROUP II: Beginning 8-10 weeks before radiation therapy, participants receive androgen
      suppression therapy subcutaneously (SC) or intramuscularly (IM) for up to 6 months (at the
      discretion of the treating physician). Participants then undergo hypofractionated radiation
      therapy as Group I.

      GROUP III: Participants receive androgen suppression therapy as Group II for up to 18 months
      (at the discretion of the treating physician), then undergo hypofractionated radiation
      therapy over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.

      After completion of study treatment, participants are followed up at 3 and 12 months, every 6
      months for 2 years, annually for 3 years, then biennially thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (hypofractionated radiation therapy)ExperimentalParticipants undergo hypofractionated radiation therapy over 15-30 minutes every other day over 2 weeks, for 5 treatments.
    Group II (radiation therapy, androgen suppression therapy)ExperimentalBeginning 8-10 weeks before radiation therapy, participants receive androgen suppression therapy SC or IM for up to 6 months (at the discretion of the treating physician). Participants then undergo hypofractionated radiation therapy as Group I.
    • Androgen Suppression
    Group III (radiation therapy, androgen suppression therapy)ExperimentalParticipants receive androgen suppression therapy as Group II for up to 18 months (at the discretion of the treating physician), then undergo hypofractionated radiation therapy over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.
    • Androgen Suppression

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed prostate adenocarcinoma at the time of surgery
    
              -  Pathologic stages T2-T3b, N0-Nx-N1, M0-1 as staged by the pathology report (American
                 Joint Committee on Cancer [AJCC] criteria 8th edition [Ed.])
    
              -  One or more high risk features including: seminal vesicle invasion, extracapsular
                 extension, positive margins, or a PSA post surgery between 0.2 and < 2.0
    
              -  PSA values < 2 ng/ml within 90 days prior to enrollment. Obtained at least 6 weeks
                 after surgery
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 assessed within 90
                 days of enrollment
    
              -  Patients must sign Institutional Review Board (IRB) approved study specific informed
                 consent
    
              -  Patients must complete all required pre-entry tests within the specified time frames
    
              -  Patients must be able to start treatment (androgen suppression [AS] or radiation)
                 within 120 days of study registration
    
              -  Positron emission tomography (PET) scan is suggested for a PSA >= 0.2 ngs/ml
    
              -  Magnetic resonance imaging (MRI) pelvis, computed tomography (CT) pelvic, or bone scan
                 for a PSA >= 0.2 ngs/ml may be done, based on the physician preference
    
              -  Members of all races and ethnic groups are eligible for this trial
    
              -  Patients from outside of the United States may participate in the study
    
            Exclusion Criteria:
    
              -  Previous pelvic radiation
    
              -  Prior androgen suppression therapy for prostate cancer for more than 6 months
    
              -  Active rectal diverticulitis, Crohn?s disease affecting the rectum or ulcerative
                 colitis (non-active diverticulitis and Crohn?s disease not affecting the rectum are
                 allowed)
    
              -  Prior systemic chemotherapy for prostate cancer
    
              -  History of proximal urethral stricture requiring dilatation
    
              -  Current and continuing anticoagulation with warfarin sodium (coumadin), heparin, low-
                 molecular weight heparin, Clopidogrel bisulfate (plavix), or equivalent (unless it can
                 be stopped to manage treatment related toxicity, to have a biopsy if needed, or place
                 markers)
    
              -  Major medical, addictive or psychiatric illness which in the investigator?s opinion,
                 will prevent the consent process, completion of the treatment and/or interfere with
                 follow-up. (Consent by legal authorized representative is not permitted for this
                 study)
    
              -  Evidence of any other cancer within the past 5 years and < 50% probability of a 5 year
                 survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell
                 cancer of the skin is allowed)
    
              -  History of myocardial infarction or decompensated congestive heart failure (CHF)
                 within the last 6 months
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Freedom from failure (FF) defined as the first occurrence of clinical failure (local recurrence, regional recurrence, or distant metastasis), the start/re-start of salvage therapy including androgen suppression, and biochemical failure (PSA >= 0.5 ng/ml)
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

    Secondary Outcome Measures

    Measure:Acute grade 2 or higher and grade 3 or higher genitourinary (GU) and gastrointestinal (GI) toxicity performed using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Descriptive measurements of frequency will be compiled. The maximum grade for each type of acute adverse events (AE) will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Similarly, grade 3 or higher GU and GI events will be estimated along with overall toxicity.
    Measure:Grade 2 or higher and grade 3 or higher GI and GU toxicity performed using NCI-CTCAE version 4 criteria
    Time Frame:3 years
    Safety Issue:
    Description:The maximum grade for each type of acute adverse events (AE) will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Similarly, grade 3 or higher GU and GI events will be estimated along with overall toxicity.
    Measure:Local/distant failure
    Time Frame:Start of treatment assessed up to 5 years
    Safety Issue:
    Description:Will be measured from the date of the start of treatment to the date of documented local failure as determined either by clinical exam, imaging, or by prostate rebiopsy.
    Measure:Distant metastasis
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be assessed using AJCC STAGING SYSTEM- PROSTATE, 8TH EDITION
    Measure:Quality of life (QOL) items from the Expanded Prostate Cancer Index Composite
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Summation of relative scores for quality of life items from the Expanded Prostate Index Composite (EPIC) instrument will be used to measure each individual's quality of life. The difference in mean scores will be assessed with the t-test. To assess changes in health-related QOL from baseline, a clinically significant difference will be defined as half of a standard deviation (SD) and at least a 10-point change. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Analysis will include percent change from baseline using t-tests and generalized linear models to test for changes at each time point and non-zero slope respectfully. EPIC is a validated instrument that measures urinary, bowel, and sexual function and bother. To statistically evaluate change over time, responses will be grouped by system and assigned a numeric score. The difference in mean scores will be assessed with the t-test.
    Measure:Impotence
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Summation of relative scores for sexual function items (items 31 through 39) from the Expanded Prostate Index Composite (EPIC) instrument will be used to measure each individual's quality of life. Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate. EPIC is a validated instrument that measures urinary, bowel, and sexual function and bother. To statistically evaluate change over time, responses will be grouped by system and assigned a numeric score. The difference in mean scores will be assessed with the t-test.
    Measure:Salvage androgen suppression use
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate.
    Measure:Overall survival
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals (CIs).
    Measure:Progression free survival
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will use clinical, biochemical and SAD as events. Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.
    Measure:Disease-free survival
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.
    Measure:Freedom from biochemical failure (FFBF)
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Will be estimated as the number of patients experiencing the event of interest divided by the total number of evaluable patients. 95% confidence intervals will be calculated for each estimate.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Mayo Clinic

    Last Updated

    July 23, 2019