Evaluating PD-1/PD-L1 in Locally Advanced Rectal Cancer by Quantitative Fluorescence Molecular Endoscopy — PREDICT  

Locally Advanced Rectal Carcinoma Clinical Trial

Official title: Improving Detection and Treatment of Locally Advanced Rectal Cancer by Dual Wavelength Quantitative Fluorescence Molecular Endoscopy Using Nivolumab-800CW and Durvalumab-680LT

Status Not yet recruiting

Clinical Trial Summary

Colorectal cancer (CRC) claims 10% of global cancer-related deaths annually, with rising incidence. Locally advanced rectal cancer (LARC) requires improved diagnostic techniques. This study focuses on dual-wavelength quantitative fluorescence molecular endoscopy (qFME) using PD-1/PD-L1-targeted tracers for LARC patients undergoing neoadjuvant treatment. Eighteen patients will receive nivolumab-800CW and durvalumab-680LT before qFME procedures, assessing programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression. We want to test the feasibility of qFME and ex vivo fluorescence imaging after intravenous administration of nivolumab-800CW, targeting PD-1, and durvalumab-680LT, targeting PD-L1, to visualize PD-L1 and PD-1 expression before and after CRT in LARC patients. If successful, this method can potentially be used in the future to see which patients most likely benefit from additional immunotherapy beforehand. The non-randomized, prospective phase 1 intervention explores biomarkers' role in treatment response prediction. Tracer administration poses minimal risks. Patients will not directly benefit, but the study aims to establish the utility of nivolumab-800CW and durvalumab-680LT in determining PD-1/PD-L1 expression during endoscopy.

Clinical Trial Description

Colorectal cancer (CRC) constitutes a significant global health burden, responsible for 10% of cancer-related deaths annually, with incidence rates escalating by 1-4% annually. Locally advanced rectal cancer (LARC) demands enhanced diagnostic tools, despite various existing modalities. This prospective, non-randomized, phase 1 intervention study addresses this need through dual-wavelength quantitative fluorescence molecular endoscopy (qFME) utilizing PD-1/PD-L1-targeted tracers. The primary goal is to assess the safety and feasibility of using durvalumab-680LT and nivolumab-800CW to assess PD-1 and PD-L1 expression alterations before and after neoadjuvant chemoradiotherapy (nCRT) in LARC patients.

The study's central hypothesis posits that higher PD-1/PD-L1 expression correlates with improved treatment response. To test this, eighteen LARC patients scheduled for nCRT and surgery will receive intravenous nivolumab-800CW and durvalumab-680LT, with qFME procedures conducted before and after nCRT. The tracers, labeled with different near-infrared (NIR) fluorophores (800CW and 680LT), allow separate quantification during simultaneous administration.

The study design is single-center, non-blinded, and non-randomized. Eligible patients, identified at the University Medical Center Groningen (UMCG), undergo qFME during staging endoscopy pre-nCRT and an additional procedure 2-3 weeks post-nCRT. Tracer administration precedes these procedures, involving monitoring for potential side effects. A potential third restaging endoscopy occurs 6-8 weeks post-CRT, without tracer administration, collecting biopsies.

The study population comprises eighteen LARC patients (cT3c-4, N1-2, M0) at UMCG scheduled for nCRT followed by surgery. Tracer administration involves 15 mg nivolumab-800CW and 15 mg durvalumab-680LT, with endoscopy procedures incorporating high-definition white-light endoscopy (HD-WLE), qFME, multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy, endoscopic rectal ultrasound (EUS), fine needle aspiration (FNA) biopsy, and ultrasound-guided needle biopsy single-fiber fluorescence (USNB/SFF) spectroscopy.

The main study parameters assess the safety of the combination of durvalumab-680LT and nivolumab-800CW through the evaluation of both vital signs after tracer administration and possible (severe) adverse events (SAE/AE's). Importantly, we will determine the feasibility of fluorescence molecular imaging using the GMP-produced near-infrared fluorescent tracers durvalumab-680LT and nivolumab-800CW for visualizing PD-1 and PD-L1 expression before and after nCRT in LARC patients with dedicated fluorescence imaging systems. Risks include minimal infection and hematoma risks from tracer administration, and the study offers negligible benefits to participants. The study's significance lies in establishing the utility of nivolumab-800CW and durvalumab-680LT in determining PD-1/PD-L1 expression during endoscopy for potential treatment response prediction in LARC. ;

Related Conditions & MeSH terms

• Locally Advanced Rectal Carcinoma
• Rectal Neoplasms

• NCT number: NCT06304597
• Study type: Interventional
• Source: University Medical Center Groningen
• Contact: Wouter B Nagengast, Prof.
• Phone: +31503612620
• Email: w.b.nagengast@umcg.nl
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 1, 2024
• Completion date: June 1, 2025