Partial Prostate Salvage High Dose Rate Brachytherapy (SalvageHDR)

High Dose Rate Partial Prostate Brachytherapy as Salvage Treatment for Local Failures After Previous External Beam Radiotherapy

A dose-response relationship for radiation in the management of prostate cancer is well established. Local recurrence of prostate cancer after external beam radiotherapy occurs in at least 40% of patients treated because of inability to deliver sufficient dose through external beam techniques. These patients respond well to re-irradiation using brachytherapy with about 50% of selected patients remaining free of recurrence 5 years after salvage. Advanced imaging using multiparametric Magnetic Resonance Imaging (mpMRI) allows identification of the site of recurrence, permitting partial prostate salvage brachytherapy. There is extensive literature on Low Dose Rate salvage brachytherapy but less on High Dose Rate.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Prostate Cancer
• Intervention / Treatment: Radiation: HDR partial prostate brachytherapy

Detailed Description

Appropriately selected patients with histologically documented recurrence 3 years or more after initial external beam radiotherapy will undergo mpMRI for identification of the site of recurrence. A planning transrectal ultrasound (TRUS) will be obtained for fusion with the mpMRI and transposition of the target volume (GTV=gross tumor volume). A margin of 4.5 cm will be added to the GTV to create a focal planning target volume (PTV). The margin may be cropped at the interface with critical organs. Two fractions of HDR brachytherapy will be delivered, each from a single implant, 2 weeks apart. Following treatment patients will be monitored for toxicity and quality of life using the Expanded Prostate cancer Index (EPIC) questionnaire as well as the International Prostate Symptom score. Efficacy will be evaluated by monitoring the Prostate Specific Antigen (PSA) and repeat mpMRI at 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juanita Crook, MD; Phone Number: 2507123958; Email: jcrook@bccancer.bc.ca

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Recruiting
      • BCCA Center for the Southern Interior
      • Sub-Investigator: Brenda Farnquist, MD
      • Sub-Investigator: Terry Bainbridge, MD
      • Principal Investigator: Juanita Crook, MD
      • Sub-Investigator: Marie-Pierre Milette, PhD
      • Sub-Investigator: David Kim, MD
      • Contact: Juanita Crook, MD; Phone Number: 250 712 3958; Email: jcrook@bccancer.bc.ca
      • Sub-Investigator: Deidre Batchelar, PhD
      • Sub-Investigator: David Petrik, MD
      • Sub-Investigator: Michelle Hilts, PhD
      • Sub-Investigator: Ross Halperin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >45 and Life expectancy >10 years
• Previous External Beam Radiotherapy (EBRT) dose up to 78Gray/39 fractions, 81 Gray/45 fractions or 70 Gray/28 fractions
• > 3 year interval since EBRT
• No late toxicity from prior EBRT > grade 2
• Rising PSA post EBRT > nadir + 2 ng/ml but < 10 ng/ml
• PSA Doubling time > 6 months
• Negative staging with CT scan of the abdomen/pelvis and bone scan
• Able to undergo multiparametric MRI with endorectal coil
• Radiographic evidence of dominant intraprostatic lesion (DIL) as only area of recurrence (i.e unifocal recurrence) and corresponding to site of original disease
• Biopsy confirmation of DIL with pathology review by British Columbia Cancer Agency GenitoUrinary pathologist (TB)
• Willing to provide informed consent
• History and physical examination within 90 days of registration
• ECOG performance status 0-1 prior to registration
• IPSS < 16, or adequate voiding study (post void residual < 100cc and peak flow rate > 10 cc/second).
• No prior trans urethral prostatic resection
• Recurrence suitable for implant with HDR brachytherapy as assessed on ultrasound simulation (maximum PTV ideally < 65% of prostate volume)
• No history of inflammatory bowel disease or previous rectal surgery
• Suitable for procedure under anesthesia, spinal or general
• INR <2.5 and platelet count >75 x 109/L
• Androgen Deprivation Therapy may be initiated at the discretion of the treating oncologist

Exclusion Criteria:

• Not compliant with criteria above
• Unable to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HDR partial prostate brachytherapy; 2 fractions of high dose rate prostate brachytherapy will be delivered to the site of recurrent disease as determined by mp-MRI	Radiation: HDR partial prostate brachytherapy; temporary radioactive implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late adverse gastrointestinal or genitourinary events grade 3 or higher	Common Terminology Criteria for Adverse Events (CTCAE V4.0)	3-60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Quality of Life	Expanded Prostate Cancer Index (EPIC)	3-60 months
Late lower urinary tract symptoms	International Prostate Symptom Score	3-60 months
Acute grade 3 or higher gastrointestinal or genitourinary adverse events	Common Terminology Criteria for Adverse Events (CTCAE V4.0)	0-3 months
Acute Quality of Life changes	Expanded Prostate Cancer Index (EPIC)	0-3 months
Acute lower urinary symptoms	International Prostate Symptoms Score	0-3 months
Biochemical disease free survival	PSA < 0.4 ng/ml at 60 months	60 months

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Investigators: Study Director: Mira Keyes, MD, BCCA

Publications and helpful links

General Publications

• Crook J, Ots A, Gaztanaga M, Schmid M, Araujo C, Hilts M, Batchelar D, Parker B, Bachand F, Milette MP. Ultrasound-planned high-dose-rate prostate brachytherapy: dose painting to the dominant intraprostatic lesion. Brachytherapy. 2014 Sep-Oct;13(5):433-41. doi: 10.1016/j.brachy.2014.05.006. Epub 2014 Jun 20.
• Arrayeh E, Westphalen AC, Kurhanewicz J, Roach M 3rd, Jung AJ, Carroll PR, Coakley FV. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e787-93. doi: 10.1016/j.ijrobp.2011.11.030. Epub 2012 Feb 11.
• Banerjee R, Park SJ, Anderson E, Demanes DJ, Wang J, Kamrava M. From whole gland to hemigland to ultra-focal high-dose-rate prostate brachytherapy: A dosimetric analysis. Brachytherapy. 2015 May-Jun;14(3):366-72. doi: 10.1016/j.brachy.2014.12.007. Epub 2015 Feb 10.
• Da Rosa MR, Milot L, Sugar L, Vesprini D, Chung H, Loblaw A, Pond GR, Klotz L, Haider MA. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging. 2015 Jan;41(1):220-5. doi: 10.1002/jmri.24710. Epub 2014 Jul 21.
• Mason J, Al-Qaisieh B, Bownes P, Thwaites D, Henry A. Dosimetry modeling for focal high-dose-rate prostate brachytherapy. Brachytherapy. 2014 Nov-Dec;13(6):611-7. doi: 10.1016/j.brachy.2014.06.007. Epub 2014 Jul 29.
• Rose JN, Crook JM, Pickles T, Keyes M, Morris WJ. Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity. Brachytherapy. 2015 May-Jun;14(3):342-9. doi: 10.1016/j.brachy.2015.01.002. Epub 2015 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 11, 2017

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; mpMRI; salvage HDR brachytherapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: H17-01641

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No