View Clinical Trial (Medical Research Study)
Hypofractionated Adaptive Image-Guided Radiation Therapy for Localized Adenocarcinoma of the Prostate
| City: |
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Baltimore |
| State: |
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Maryland |
| Zip Code: |
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21231 |
| Conditions: |
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Prostate Cancer |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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Inclusion Criteria:
- Histologically confirmed, locally confined adenocarcinoma of the prostate
- Clinical stages T1a to T2c PSA of less than 20 ng per ml
- Gleason score of less than 8
- 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 8 or higher score
- PSA greater than 20 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
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| NCT ID: |
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NCT00809991 |
| Primary Contact: |
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Principal Investigator
Danny Song, MD
The Johns Hopkins University School of Medcine
Shirl DiPasquale, RN
Phone: 410-614-1598
Email: sdipasq1@jhmi.edu
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| Backup Contact: |
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Danny Song, MD
Phone: 410-502-5875
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| Location Contact: |
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Baltimore, Maryland 21231
United States
Shirl DiPasquale, RN
Phone: 410-614-3158
Email: sdipasq1@jhmi.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 21, 2013 |
| Modifications to this listing: |
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