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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00809991
Recruitment Status : Recruiting
First Posted : December 17, 2008
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE December 16, 2008
First Posted Date  ICMJE December 17, 2008
Last Update Posted Date March 13, 2020
Actual Study Start Date  ICMJE December 22, 2008
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2013)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2008)
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 3.2 Gy per day to a total dose of 67.2 Gy (21 fractions). [ Time Frame: 7 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2008)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate
Official Title  ICMJE Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Radiation: hypofractionation
3.6 Gy per day to a total dose of 57.6 Gy (16 fractions). T
Study Arms  ICMJE Experimental: Hypofractionated radiation therapy in prostate adenocarcinoma
Participants 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).
Intervention: Radiation: hypofractionation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2008)
188
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shirl DiPasquale, RN 410-614-1598 sdipasq1@jhmi.edu
Contact: Danny Song, MD 410-502-5875
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00809991
Other Study ID Numbers  ICMJE J0859
NA_00019393 ( Other Identifier: JHM IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Danny Song, MD The Johns Hopkins University School of Medcine
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP