Clinical Trials /

Image-guided Focal Brachytherapy Utilizing Combined 18F-DCFPyl PET/CT

NCT03861676

Description:

The Principal Investigator's (PI) working hypothesis is that the PI can utilize the high predictive value of 18F-DCFPyl PSMA to identify clinically significant tumors in patients who will undergo brachytherapy, as well as areas which are uninvolved or contain only clinically insignificant disease. In the PI's clinical trial, the uninvolved regions (as defined by combined PET-MR-biopsy data) will not be targeted and receive only fall-off dose, which we have shown to be associated with reductions in toxicity.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Image-guided Focal Brachytherapy Utilizing Combined 18F-DCFPyl PET/CT
  • Official Title: Image-guided Focal Brachytherapy Utilizing Combined 18F-DCFPyl PET/CT and Dynamic Dosimetry With Registered Ultrasound and Fluoroscopy for Localized Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: J1889
  • SECONDARY ID: IRB00173561
  • SECONDARY ID: R01CA151395
  • NCT ID: NCT03861676

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
(18F)DCFPyLPSMA, PETFocal brachytherapy

Purpose

The Principal Investigator's (PI) working hypothesis is that the PI can utilize the high predictive value of 18F-DCFPyl PSMA to identify clinically significant tumors in patients who will undergo brachytherapy, as well as areas which are uninvolved or contain only clinically insignificant disease. In the PI's clinical trial, the uninvolved regions (as defined by combined PET-MR-biopsy data) will not be targeted and receive only fall-off dose, which we have shown to be associated with reductions in toxicity.

Detailed Description

      Current conventional prostate cancer (PCa) imaging modalities (computed tomography, bone
      scan, magnetic resonance imaging, ultrasound) have limited accuracy in the initial staging
      and for determining prognosis of PCa. Prostate-specific membrane antigen (PSMA) is a cell
      surface antigen which is highly expressed in PCa and correlates with prognostic factors such
      as Gleason score. High PSMA expression in prostate tumor has been significantly associated
      with lethality of disease, allowing specific identification of tumors most in need of
      treatment. Combined PET and computed tomography (PET-CT) imaging using small molecules
      targeting PSMA-expressing cells have been developed and tested clinically, and have shown
      superiority when compared with conventional imaging.

      An added advantage of PET compared to MRI is the ability to identify both distant metastatic
      disease as well as intraprostatic disease with one imaging modality. PSMA-radiotracers have
      continued to evolve since their initial development, with successive improvements in imaging
      and diagnostic characteristics. One such second-generation PSMA-binding compound, 18F-DCFPyl,
      has been developed and characterized at our institution, and offers superior imaging
      qualities compared to prior PSMA-based radiotracers.

      In realization of the toxicity of current therapies, there is substantial interest throughout
      the urologic oncology community in utilizing focal therapy to mitigate such toxicities. The
      rationale for focal therapy is based upon the recognition that whole gland treatment is
      associated with unacceptable toxicity rates, while concurrently it is also realized that
      patient morbidity and mortality is due to the progression of major foci of high-grade
      disease, i.e. the index lesion.

      Planning studies have shown that focal brachytherapy is feasible and results in significant
      reductions of dose to critical structures. In a historic cohort of patients treated at Johns
      Hopkins, the investigators have demonstrated that a modest reduction in dose results in
      clinically meaningful reductions in urinary toxicity. Al-Qaiseh et al. found that focal plans
      resulted in >50% reductions in dose to urethra and rectum. However, focal plans were highly
      sensitive to seed positioning errors, and focal targeting made seed positioning more
      critical. This highlights the key utility and importance of the investigators' iRUF system
      (integrated Registered Fluoroscopy and Ultrasound) in delivering focal therapy.

      The investigators have developed a system of true dynamic intraoperative dosimetry which
      utilizes fluoroscopy for seed cloud reconstruction and fusion to transrectal ultrasound
      imaging. The investigators previously confirmed this method in a pilot trial of 6 patients
      with encouraging results. Further refinement of the system was followed by a Phase II
      clinical trial of this integrated platform on a larger group of patients. The investigators
      confirmed the primary endpoint to compare intraoperative dosimetric predicted values using
      iRUF method vs standard ultrasound-based seed tracking. The iRUF Phase II cohort had
      statistically significant improvements in prostate coverage parameters, as well as lower
      rates of rectal doses exceeding prescribed tolerance limits when compared to a historical
      group of patients. Importantly, there was no trend toward higher prostate V200 doses,
      indicating that excellent coverage did not come at the expense of excessive dose within
      prostate.

      This study will test the combination of PSMA-imaging with iRUF dynamic dosimetry to treat
      prostate cancer with a focal approach.
    

Trial Arms

NameTypeDescriptionInterventions
Focal brachytherapyExperimentalDrug: 18F-DCFPyl Other names: PET, PSMA Procedure: Focal brachytherapy with PSMA PET imaging Other names: Radiotherapy, Radiation, Prostate seed implant, Focal therapy
  • (18F)DCFPyL

Eligibility Criteria

        Inclusion Criteria:

          -  Adenocarcinoma of the prostate

          -  Performance Status < 2

          -  Clinical stages (not radiographic stage) T1c - T2a, Nx or N0, Mx or M0

          -  Gleason 6-7 cancer

          -  Prostate volume < 60 cc (if MRI and TRUS have conflicting values, then MRI value will
             be utilized)

          -  International Prostate symptom score (IPSS) 20 or less

          -  Ability to undergo DCF-Pyl PSMA PET as part of pretreatment staging

          -  Signed study-specific consent form prior to registration

        Exclusion Criteria:

          -  Prior history of pelvic radiation therapy

          -  Major medical or psychiatric illness which, in the investigator's opinion, would
             prevent completion of treatment and would interfere with follow up.

          -  Implanted device or apparatus which obstruct visibility of the implanted sources on
             fluoroscopy

          -  Metallic implants, claustrophobia not amenable to medication, or known
             contraindications to undergoing MR scanning

          -  History of other malignancy diagnosed within the past 3 years
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percent tumor coverage
Time Frame:Post-implant Day 30
Safety Issue:
Description:Percent coverage of the combined PET-MR based tumor volume achieved when using iRUF intraoperative dosimetry. PET-MR tumor volume D90 will be defined on pre-treatment PET-MR fusion, and dose from seeds will be calculated on post-implant MR/CT (Day ~30); the two volumes will be co-registered to determine tumor volume coverage.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • focal therapy
  • brachytherapy
  • PSMA
  • DCF-Pyl

Last Updated

November 26, 2019