High Dose Rate Prostate Brachytherapy: Dose Escalation to Dominant Intra-prostatic Nodule (Dosepainting)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by British Columbia Cancer Agency
Sponsor:
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT01605097
First received: May 22, 2012
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

This study will investigate the feasibility of using technology of ultrasound guided HDR brachytherapy to focally increase dose to regions within the prostate that are heavily infiltrated with cancer. Such regions, referred to as "dominant intraprostatic lesions" or DILs can be visualized using diffusion contrast enhanced MRI employing an endo-rectal coil. The MR images can be fused with the planning transrectal ultrasound (TRUS) prior to the brachytherapy procedure to design a dose distribution that will encompass the malignant volume with higher than the prescription dose. By its nature, brachytherapy has subvolumes that receive (for example)125% of the prescription dose or 150% of the prescription dose. With TRUS-guided and TRUS-planned HDR these areas can be manipulated to coincide with the DIL. The limit of dose escalation has been reached at whole prostate external beam doses of 81-86 Gy and still failure rates for intermediate and high risk disease are unacceptable. There is much interest in focal dose escalation and TRUS-guided HDR brachytherapy is perfectly suited to achieving this.


Condition Intervention Phase
Prostate Cancer
Radiation: HDR interstitial brachytherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Rate Prostate (HDR) Brachytherapy Dose Escalation to Dominant Intra-prostatic Nodule for Patients With Intermediate and High Risk Prostate Cancer

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • Feasibility of delivery of a higher than prescription dose to the dominant intra-prostatic nodule as defined on diffusion contrast-enhanced endo-rectal MRI, while respecting tolerance doses of adjacent normal organs. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Data to be collected are:

    i) ratio of volume of GTV to prostate volume ii) number of DIL's per prostate iii) isodose encompassing DIL without exceeding critical organ dose constraints (Urethral volume receiving 115%= 0, Dose to 1cc of rectal wall < 7 Gy)



Secondary Outcome Measures:
  • Acute toxicity compared to a cohort of 25 patients treated to standard dose [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

    Data to be collected are:

    i) urinary retention rate and duration ii) maximum International Prostate Symptom Score and time to normalize iii) rectal toxicity


  • Efficacy will be assessed by repeat DCE MRI at 12 months and TRUS-guided prostate biopsy at 30 months. [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Repeat DCE endorectal MRI will be repeated at one year post treatment to assess imaging response. Histologic response will be assessed at 30 months as studies have shown that this is the otpimal time for post radiotherapy prostate biopsy.


Estimated Enrollment: 15
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HDR interstitial brachytherapy
HDR prostate brachytherapy with dose escalation to 1250 cGy to the MRI-defined dominant intraprostatic lesion
Radiation: HDR interstitial brachytherapy
2 treatments of 1000 cGy will be delivered to the entire prostate volume while escalating the dose to the visible disease to 1250 cGy
Other Name: Planning soft ware Varian Medical Systems Vitesse III

Detailed Description:

Methods: If a dominant nodule is visualized on DCE MRI, it will be contoured in 3D and the images fused to the planning TRUS study that is done in preparation for brachytherapy (of any type: seeds or HDR). The patient's treatment will consist of the standard combined external beam (4600 cGray in 23 fractions) and HDR brachytherapy boost (2 fractions of 1000 cGray given on days 5 and 15 of the external beam course). During each HDR treatment the plan will be manipulated such that the normally occurring high dose regions (125%, 150%) are positioned at the site of the identified disease. Normally approximately 60% of the prostate volume receives 125% of the dose and 30% receives 150%. By ensuring that the inherent dosimetry favors treatment of the known cancer, no region of the prostate would be "underdosed". HDR treatments are performed under general anesthesia as an out patient procedure.

Statistical Analysis: This is a feasibility study and the data reported will be descriptive including the frequency with which the DIL can be visualized in this population, the DIL volume compared to total prostate volume, and the isodose that can encompass the DIL without violating dose constraints to adjacent organs (urethra and bladder). Toxicity will be monitored and efficacy will be assessed by repeat DCE MRI at 12 months and biopsy at 30 months.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically proven adenocarcinoma of the prostate
  • intermediate or high risk prostate cancer

    • Intermediate risk prostate cancer patients must have:

      • Clinical stage ≤ T2c,
      • Gleason score = 7 and iPSA ≤ 20, or
      • Gleason score ≤ 6 and iPSA > 10 and ≤ 20.
    • High risk patients may have

      • Clinical stage T3
      • Gleason score 8-10
      • PSA > 20 ng/ml
  • fit for general anesthetic.
  • unilateral disease with either a palpable nodule or a cluster of positive biopsies from a single region suggesting the presence of dominant nodule.
  • estimated life expectancy of at least 10 years.
  • ECOG performance status of 0 - 2.
  • no contraindications to interstitial prostate brachytherapy.
  • if on coumadin therapy must be able to stop safely for 7 days.
  • must not have any contraindications to MRI

Exclusion Criteria:

  • Does not meet staging criteria for intermediate or high risk prostate cancer
  • Does not have a localized high volume of intraprostatic disease
  • unfit for general anesthetic
  • MRI contraindicated
  • unable to stop blood thinners
  • Life expectancy < 10 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605097

Contacts
Contact: Juanita M Crook, MD 250 712 3979 jcrook@bccancer.bc.ca
Contact: Francois Bachand, MD 250 712 3900 fbachand@bccancer.bc.ca

Locations
Canada, British Columbia
Cancer Center for the Southern Interior Recruiting
Kelowna, British Columbia, Canada, V1Y5L3
Principal Investigator: Juanita M Crook, MD         
Sub-Investigator: Francois Bachand, MD         
Sponsors and Collaborators
British Columbia Cancer Agency
Investigators
Principal Investigator: Matthew Schmid, MSc Medical Physicst
  More Information

Publications:
Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT01605097     History of Changes
Other Study ID Numbers: H12-00557
Study First Received: May 22, 2012
Last Updated: June 20, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by British Columbia Cancer Agency:
prostate neoplasms
interstitial radiation
High dose rate prostate brachytherapy
dose escalation

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 24, 2014