Trial Status: Open to Recruitment
This is a single-centre study in those with high-risk prostate cancer.
(Dose 5 mg; Interval 96 h) Example of imaging of a large node with positive intraoperative fluorescence in Patient 15. Panel A: White light illumination: AL 1: Internal iliac lymph node; AL 2: Left obturator nerve and vessels; Panel B: NIR Fluorescence excitation; Panel C: H&E stain; Panel D: Adjacent section, PSMA IHC stain; E: Adjacent section, tissue NIR Fluorescence
SUMMARY
ProMOTE is a single centre evaluation in men diagnosed with high-risk prostate cancer who are eligible for robot-assisted laparoscopic radical prostatectomy (RARP) by local standard of care. The evaluation uses a marker and dye combination which is aimed to bind to prostate cancer cells and make them shine under a special camera. We believe this will help surgeons to see cancer cells, to help them remove all prostate cancer, whilst avoiding removing healthy tissue unnecessarily. Stage 1 of this trial has been completed (a first in human dose optimisation stage in 24 participants) and we are currently conducting Stage 2 randomised controlled trial which has recruited so far 29 out of 120 planned participants.
We developed cutting-edge real-time optical imaging based on multiple, solid-state sources and a single specialised high sensitivity imager. The system is uniquely sensitive, providing fluorescence images in near real-time, simultaneously with conventional white light reflectance, by selectively preventing the fluorescence excitation light from reaching the imager. This complements the recent development of a fluorescently labelled compound that can specifically bind to the surface of PC cells. This places us in a unique position to test these imaging techniques in patients with high-risk PC, to determine their value in improving staging to guide ‘precision surgery’.
The Investigational Medicinal Product (IMP) used in this evaluation is IR800-IAB2M - an anti- Prostate specific membrane antigen (PSMA) IAB2M minibody conjugated to the fluorescent IRDye800CW dye. It has been developed by our collaborator ImaginAb, Inc.
This evaluation is sponsored by the University of Oxford and conducted by SITU and OCTRU and jointly by the NDS and Oncology Departments. It is funded by the CRUK Programme Grant A18444 and supported the BRC Surgical Theme. Prof. Freddie Hamdy is the Chief Investigator.
AIMS AND OBJECTIVES
Stage 1
Primary objective:
Determine the optimal dose and timing of IMP administration
Primary outcome measure:
Visibility of lesions at surgery including autofluorescence
Stage 2
Primary objective:
Increase in rate of complete excision of cancerous tissue and negative surgical margins
Primary outcome measure:
Histopathological assessment
STUDY DESIGN
This is an evaluation of molecular imaging techniques in intermediate and high-risk prostate cancer (PC) patients using deep red/near-infrared (NIR) fluorescence imaging with a fluorescent imaging molecule during robot-assisted laparoscopic radical prostatectomy (RARP) to define extra-capsular and nodal involvement and optimise the extent of surgical resection.
This evaluation is done in 2 stages:
Stage 1: Optimisation of dose administration, pre-operative interval and equipment in up to 24 participants with high-risk disease, using different combinations of IR800-IAB2M doses and time intervals between administration of the compound and RARP surgery.
This is now completed and has been published in the European Journal of Nuclear Medicine and Molecular Imaging.
Stage 2: Prospective validation with optimized dose and time interval to evaluate the benefit of peri-operative molecularly-targeted imaging by comparing two matched groups of participants with intermediate or high-risk untreated PC both receiving either conventional RARP, one with molecular imaging and one without (control group). In order to remove bias in participant selection we will use randomisation to allocate participants to these two groups.