Clinical trial NCT01605097: High Dose Rate Prostate Brachytherapy: Dose Escalation to Dominant Intra-prostatic Nodule
Official title: High Dose Rate Prostate (HDR) Brachytherapy Dose Escalation to Dominant Intra-prostatic Nodule for Patients With Intermediate and High Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: prostate neoplasms
interstitial radiation
High dose rate prostate brachytherapy
dose escalation
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
First posted: 2012-05-24
Enrollment: 26
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 (DIL) can be visualized using diffusion contrast enhanced MRI employing an endo-rectal coil. The magnetic resonance (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.

Detailed description: Methods: If a dominant nodule is visualized on dynamic contrast enhanced (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 centiGray (cGy) in 23 fractions) and HDR brachytherapy boost (2 fractions of 1000 cGy 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 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 initial prostate specific antigen (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.
* Eastern Cooperative Oncology Group (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

Primary outcomes:
measure: Average Mean Dose to 90% of DIL Volume
timeFrame: 12 months
Secondary outcomes:
measure: Acute Toxicity
timeFrame: 24 months
measure: Prostate Specific Antigen(PSA) Response at 5-years
timeFrame: 5 years
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: Cancer Center for the Southern Interior
state: British Columbia
Study officials:
affiliation: Medical Physicst
name: Matthew Schmid, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Groenendaal G, van den Berg CA, Korporaal JG, Philippens ME, Luijten PR, van Vulpen M, van der Heide UA. Simultaneous MRI diffusion and perfusion imaging for tumor delineation in prostate cancer patients. Radiother Oncol. 2010 May;95(2):185-90. doi: 10.1016/j.radonc.2010.02.014. Epub 2010 Mar 16.
citation: Kim Y, Hsu IC, Lessard E, Kurhanewicz J, Noworolski SM, Pouliot J. Class solution in inverse planned HDR prostate brachytherapy for dose escalation of DIL defined by combined MRI/MRSI. Radiother Oncol. 2008 Jul;88(1):148-55. doi: 10.1016/j.radonc.2007.11.024. Epub 2008 Feb 20.
citation: Pouliot J, Kim Y, Lessard E, Hsu IC, Vigneron DB, Kurhanewicz J. Inverse planning for HDR prostate brachytherapy used to boost dominant intraprostatic lesions defined by magnetic resonance spectroscopy imaging. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1196-207. doi: 10.1016/j.ijrobp.2004.02.055.
citation: De Bari B, Daidone A, Alongi F. Is high dose rate brachytherapy reliable and effective treatment for prostate cancer patients? A review of the literature. Crit Rev Oncol Hematol. 2015 Jun;94(3):360-70. doi: 10.1016/j.critrevonc.2015.02.003. Epub 2015 Feb 17.