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Trial Title:
Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate
NCT ID:
NCT00809991
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Adenocarcinoma
Conditions: Keywords:
Prostate Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
hypofractionation
Description:
3.6 Gy per day to a total dose of 57.6 Gy (16 fractions). T
Arm group label:
Hypofractionated radiation therapy in prostate adenocarcinoma
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.
Criteria for 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The Johns Hopkins University School of Medicne
Address:
City:
Baltimore
Zip:
21231
Country:
United States
Start date:
December 22, 2008
Completion date:
September 2025
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT00809991