Clinical Trials /

Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate

NCT00809991

Description:

This will be a Phase II study evaluating the effectiveness and toxicity of a specific radiation therapy regimen. This choice of daily dose is based on the prior published experience showing safety and efficacy of hypofractionated regimens. The total dose is calculated to be effective for late effects which has been shown to be effective and safe in a large prospective Phase II study. If the hypothesis for the prostate is is true, then this regimen should be at least as effective or more effective for tumor control than the current conventional therapy.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate
  • Official Title: Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate

Clinical Trial IDs

  • ORG STUDY ID: J0859
  • SECONDARY ID: NA_00019393
  • NCT ID: NCT00809991

Conditions

  • Prostate Cancer

Purpose

This will be a Phase II study evaluating the effectiveness and toxicity of a specific radiation therapy regimen. This choice of daily dose is based on the prior published experience showing safety and efficacy of hypofractionated regimens. The total dose is calculated to be effective for late effects which has been shown to be effective and safe in a large prospective Phase II study. If the hypothesis for the prostate is is true, then this regimen should be at least as effective or more effective for tumor control than the current conventional therapy.

Detailed Description

      Radiation therapy is an effective and frequently utilized modality for the treatment of
      clinically localized prostate cancer. Traditionally, external beam radiation has been
      delivered in a fractionated manner using daily doses of 1.8-2.0 Gy. This daily dose was
      derived from early animal experiments and clinical experience, supported by mathematical
      models of normal tissue and tumor response to fraction size. The most widely used of these
      models is the linear-quadratic formula, which predicts responses to different fraction sizes
      based on the alpha/beta ratio of any given tissue.

      One of the main motivations for delivering a treatment at low dose rate or with many
      fractions is that late-responding normal tissue are generally more sensitive than
      early-responding tissues (i.e. tumor) to increases in fraction size. So increasing the number
      of fractions generally spares late-responding tissues more than the tumor. This can be
      quantified in terms of the alpha/beta ratio:

        -  Small alpha/beta ratio (2-4 Gy), typical of late sequelae, means high sensitivity to
           fractionation changes.

        -  Large alpha/beta ratio (>8 Gy), typical of tumor control, means low sensitivity to
           fractionation changes.

      It is generally assumed that the mechanistic basis for the different fractionation response
      of tumors and late-responding normal tissues relates to the larger proportion of cycling
      cells in tumors. But prostate tumors contain unusually small fractions of cycling cells.
      Brenner and Hall as well as Duchesne and Peters have reasoned that prostate tumors might not
      respond to changes in fractionation in the same way as other cancers; both papers hypothesize
      that prostate tumors might respond to changes in fractionation or dose rate more like a
      late-responding normal tissue. , In mathematical terms, the suggestion is that the alpha/beta
      ratio for prostate cancer might be low, comparable to that for late-responding tissues or
      even lower. Previous estimates of alpha/beta ratios of normal tissue and tumor tissue have
      generally been 3 and 10, respectively. Recent evidence has estimated the alpha/beta ratio of
      prostate cancer to be as low as 1.5. If these hypotheses are true, then the optimal
      therapeutic ratio for prostate cancer would be achieved using daily doses higher than 2 Gy.

      Several preliminary clinical reports have found reasonable PSA control rates and no increase
      in late toxicity using doses of 2.5 to 3 Gy. Kupelian from the Mayo Clinic found PSA-free
      survival rates of 97%, 88%, and 70% in low-, intermediate-, and high-risk patients,
      respectively. The dose regimen used was 70 Gy in 2.5 Gy daily fractions. Both acute and late
      toxicity were not higher than seen with typical dose regimens. A group from Christie Hospital
      reported 82%, 56%, and 39% 5-year biochemical disease free survival rates (low, intermediate,
      and high risk, respectively) in patients treated with 50 Gy in 16 fractions (3.125 Gy per
      fraction), with acceptable bowel and bladder toxicity.

      These results, although promising, require further validation. If the hypothesis that
      prostate cancer alpha/beta ratio is lower than normal tissue is correct, then the optimal
      fractional dose is likely to be even higher than the doses tested thus far, but if incorrect,
      the result may be increased normal tissue toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Hypofractionated radiation therapy in prostate adenocarcinomaExperimentalParticipants with histologically confirmed, locally confined adenocarcinoma of the prostate receive 3.6 Gy per day to a total dose of 57.6 Gy (16 fractions).

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed, locally confined adenocarcinoma of the prostate
    
              -  Clinical stages T1a to T2b PSA of less than 10 ng per ml
    
              -  Gleason score of less than 3+4=7
    
              -  The patient has decided to undergo external beam radiation as treatment choice for his
                 prostate cancer
    
              -  Signed study-specific consent form prior to registration
    
            Exclusion Criteria:
    
              -  Stage T3 to 4 disease
    
              -  Gleason 4+3=7 or higher score
    
              -  PSA greater than 10 ng per ml
    
              -  Clinical or Pathological Lymph node involvement N1
    
              -  Evidence of distant metastases M1
    
              -  Radical surgery for carcinoma of the prostate
    
              -  Previous Chemotherapy or pelvic radiation therapy
    
              -  Previous or concurrent cancers other than basal or squamous cell skin cancers or
                 superficial bladder cancer unless disease free for at least 5 years
    
              -  History of inflammatory bowel disease
    
              -  Major medical or psychiatric illness which, in the investigator's opinion, would
                 prevent completion of treatment and would interfere with follow up
          
    Maximum Eligible Age:100 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Assess the incidence of grade 2 or greater GU and GI toxicity and self-reported quality of life data with image-guided radiation therapy in doses of 3.6 Gy per day to a total dose of 57.6Gy (16 fractions).
    Time Frame:7 years
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Assess biochemical and clinical control rates associated with the hypofractionated dose regimen for both low-risk and intermediate-risk groups. Assessment will be performed at median 4 years and again at median 7 years' follow-up.
    Time Frame:7 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Trial Keywords

    • Prostate Cancer

    Last Updated

    March 13, 2019