Clinical trial NCT01578902: Hypofractionated Accelerated Radiotherapy for Low Risk Localized Prostate Cancer
Official title: Hypofractionated Accelerated Radiotherapy for Low Risk Localized Prostate Cancer (pHART 3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostatic Neoplasms
Radiotherapy
Hypofractionation
Low Risk Prostate Cancer
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Canadian Association of Radiation Oncology
First posted: 2012-04-17
Enrollment: 84
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of a short course of radiotherapy (35 Gy / 5 fractions / 29 days) for the treatment of low-risk prostate cancer.

Detailed description: Rationale for Proposed Study With the availability of intensity modulated radiotherapy (IMRT) at the Odette Cancer Centre (OCC), there is an opportunity to explore the use of a much more intensive hypofractionation schedule for prostate cancer. Using an alpha/beta ratio of 1.3, a dose of 35 Gy in 5 fractions would be equivalent to 88 Gy delivered in 2 Gy fractions. For normal tissues (alpha/beta value of 2), this would be equivalent to 78 Gy in 2 Gy fractions. As such, the linear quadratic equation predicts that 35 Gy in 5 fractions should not result in any increased late toxicity for normal tissues compared to standard dose escalated radiotherapy. However, the biological dose to the prostate cancer would be significantly increased. As a safety precaution for this study proposal, the investigators propose to deliver 35 Gy in 5 fractions over 5 weeks (one radiotherapy fraction of 7 Gy per week) to allow for normal tissue repair.

With IMRT, it is expected that there will be superior conformality of the high dose region around the target volume. As well, the use of daily on-line imaging will allow us to eliminate interfraction prostate motion errors and use tighter planning target volume margins for any residual intrafraction motion. At OCC, such an approach has already been shown to be feasible and is currently employed in the phase 1/2 concomitant boost study for high risk prostate cancer.

If proven to be safe and effective, such a hypofractionated radiotherapy schedule may have significant practical advantages as well. With only 1 fraction of radiotherapy delivered each week (for a total of 5 weeks), there are huge savings in resource utilization and increased convenience for patients.

The investigators propose to start a small phase 1 study to explore the use of this dose fractionation for men with low risk prostate cancer. The primary endpoint for this small pilot study would be acute and late normal tissue toxicities. If proven to be feasible and safe, external peer-reviewed funding will be sought to further explore this novel treatment schedule in a larger phase 2 setting.

Eligibility criteria: Inclusion Criteria:

* Informed consent signed (Appendix A)
* Adult men greater than 18 years of age
* Histologically confirmed diagnosis of adenocarcinoma of the prostate (centrally reviewed).
* Clinical stage T1-T2b, Gleason Score \< 6, and PSA \< 10 ng/mL
* Less than 50% of biopsy cores +ve for cancer
* Less than 50% overall surface area involved with cancer
* Neoadjuvant hormone suppression therapy is allowed. However, PSA, must have been performed within 2 months of starting androgen suppression therapy. If androgen suppression therapy has been started LHRH agonist must be continued for a minimum of 3 months before initiation of gold fiducial marker insertion \& radiotherapy planning.

Exclusion Criteria:

* Prior pelvic radiotherapy.
* Concurrent anticoagulation medication (if it is unsafe to discontinue for gold seed insertion)
* Diagnosis of bleeding diathesis
* Presence of a hip prosthesis
* Pelvic girth \>40cm (to ensure visibility of gold seeds on electronic portal imaging device)
* Large prostate (\> 60 cm3) on imaging
* Severe lower urinary tract symptoms (International Prostate Symptom Score \> 15 or nocturia \> 3)

Primary outcomes:
measure: Incidence of Grade 3+ Gastrointestinal Toxicity
timeFrame: Acute period (up to 6 months)
Secondary outcomes:
measure: Incidence of Grade 3+ Genitourinary Toxicity
timeFrame: Acute (up to 6 months) and Late (6 months and after)
measure: Incidence of Grade 3+ Rectal and Urinary Toxicity
timeFrame: Late (6 months and after)
measure: Patient Reported Quality of Life
timeFrame: up to 5 years
measure: Biochemical (ie. Prostate Specific Antigen) Disease Free Survival
timeFrame: 5 year
measure: Biopsy Positive Rate
timeFrame: 3 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Andrew Loblaw, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Patrick Cheung, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quon HC, Musunuru HB, Cheung P, Pang G, Mamedov A, D'Alimonte L, Deabreu A, Zhang L, Loblaw A. Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials. Front Oncol. 2016 Aug 29;6:185. doi: 10.3389/fonc.2016.00185. eCollection 2016.