Clinical trial NCT04004858: Prostate Margin Reduction to Reduce Acute Rectal Toxicity (PROTRACT)
Official title: Reducing Acute Rectal Toxicity for Hypofractionated Prostate Radiotherapy - An Multi-institution Pilot Study of Reduced PTV Margin
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer
Keywords: Radiation toxicity
Hypofractionation
Margin reduction
Lead sponsor: Southlake Regional Health Centre
Sponsor class: OTHER
Collaborators: name: Sunnybrook Health Sciences Centre
name: University Health Network, Toronto
First posted: 2019-07-02
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The prospective pilot study will consist of two cohorts of patients: one cohort planned with the current standard PTV margin and the second cohort planned with the reduced margin validated from the retrospective study. The first cohort will be recruited while the retrospective study is being carried out and the second cohort will be accrued once the retrospective validation is completed.
Primary purpose: TREATMENT

Brief summary: The objectives of this study are:

1. Retrospectively validate a reduced margin schema for intermediate risk prostate hypofractionated VMAT treatments
2. Demonstrate in a prospective pilot clinical trial that patients planned and treated with the reduced margin schema will have reduced acute rectal toxicity

Detailed description: Hypofractionated radiotherapy is being adopted as standard practice for intermediate risk prostate cancer patients. The objective of this project is to retrospectively validate whether reducing the Planning Target Volume (PTV), a margin placed around the prostate to account for movement and variability in patient placement, will have reduced acute rectal toxicity. The project will focus on patients with intermediate risk prostate cancer treated with hypofractionated Volumetric Modulated Arc Therapy (VMAT) from multiple institutions. The investigators intend to prospectively demonstrate that patients planned and treated with the reduced margin, along with using advanced image-guidance and consistent bladder and rectum preparation will have reduced acute rectal toxicity.

The project consists of two phases: phase one is a retrospective planning study and phase two is a prospective pilot clinical trial.

Phase one aims to validate the benefits of the proposed decrease in PTV margin by assessing whether the investigators can continue to deliver the intended radiation dose to the prostate while further sparing the rectum. This will be accomplished by evaluating the daily delivered dose on Cone-Beam Computed Tomography (CBCT), a daily scan performed during treatment that determines the location of the prostate and rectum. Using these CBCT scans, the investigators can reconstruct the radiation dose delivered to any organs of interest which was affected by their relative positions each day. There are two parts in this phase one retrospective planning study. Part one will focus on 30 intermediate risk prostate cancer cases already treated with hypofractionation (60 Gy in 20 fractions) using the standard PTV margins from all three participating institutions. All 30 cases will then be re-planned using the reduced PTV margin and dose reconstruction will be performed on daily CBCT to confirm adequate target coverage of the prostate. Part two aims to demonstrate that the reduced PTV margin can help enable hypofractionation. Thirty cases that were originally intended to receive a hypofractionated regimen of 60 Gy in 20 fractions but had to either switch to a standard fractionation treatment of 78 Gy in 39 fractions (a regimen used when 60Gy in 20 fractions is not achievable), or where there had to be compromised target coverage of the prostate, due to Organs at Risk (OAR) receiving unacceptable doses of radiation, will be selected. These cases will be re-planned with the validated smaller PTV margin to illustrate that they would now be eligible to receive hypofractionation due to the reduced dose to OARs.

Phase two aims to demonstrate that patients treated with the reduced PTV margin will have reduced acute rectal toxicity as evaluated by the Cancer Care Ontario (CCO) Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) Quality of Life (QOL) questionnaire. Two groups of patients will be accrued: one group of 25 patients will be planned and treated with the current standard PTV margin as the control group, while the second group of 25 patients will be planned and treated with the reduced PTV margin validated from the phase one retrospective study. A comparison of rectal toxicity scores between these two groups will then be carried out using the EPIC-CP questionnaire.

Eligibility criteria: Inclusion Criteria:

1. Male patients with intermediate-risk prostate cancer receiving external beam radiotherapy
2. Age greater than or equal to 18 years
3. Agreeable to proposed follow-up schedule and able to complete quality of life questionnaire as proposed

Exclusion Criteria:

1. Previous radiotherapy to the pelvic region
2. Inflammatory bowel disease or chronic colitis.
3. Connective tissue disorders such as scleroderma.
4. Patients with hip replacements

Primary outcomes:
measure: Reduced acute rectal toxicity from reduced PTV margin
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Southlake Regional Health Centre
name: Beibei Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
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