Hypofractionated Accelerated Radiotherapy for Low Risk Localized Prostate Cancer (pHART3)

Hypofractionated Accelerated Radiotherapy for Low Risk Localized Prostate Cancer (pHART 3)

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Stereotactic ablative body radiotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hypofractionated radiotherapy using SABR; Stereotactic radiation: 35Gy in 5 fractions over 29 days	Radiation: Stereotactic ablative body radiotherapy; 35Gy/5 fractions/29 days; Other Names: standard linear accelerator delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3+ Gastrointestinal Toxicity	Common Terminology Criteria for Adverse Events (CTCAE) v3.0	Acute period (up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3+ Genitourinary Toxicity	Common Terminology Criteria for Adverse Events (CTCAE) v3.0	Acute (up to 6 months) and Late (6 months and after)
Incidence of Grade 3+ Rectal and Urinary Toxicity	Common Terminology Criteria for Adverse Events (CTCAE) v3.0	Late (6 months and after)
Patient Reported Quality of Life	Expanded Prostate Cancer Index Composite (EPIC)	up to 5 years
Biochemical (ie. Prostate Specific Antigen) Disease Free Survival	Failure = Follow-up PSA greater than nadir PSA + 2 ng/ml	5 year
Biopsy Positive Rate	Patients were biopsied at 3 years post treatment	3 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Association of Radiation Oncology
• Investigators: Principal Investigator: Patrick Cheung, MD, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: October 31, 2011
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (ESTIMATE): April 17, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Radiotherapy; Hypofractionation; Prostatic Neoplasms; Low Risk Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 371-2006