nctId: NCT06304597 id: 17651 briefTitle: Evaluating PD-1/PD-L1 in Locally Advanced Rectal Cancer by Quantitative Fluorescence Molecular Endoscopy acronym: PREDICT overallStatus: NOT_YET_RECRUITING date: 2024-04-01 date: 2025-03-01 date: 2025-06-01 date: 2024-03-12 date: 2024-03-12 name: University Medical Center Groningen class: OTHER briefSummary: 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. conditions: Locally Advanced Rectal Carcinoma studyType: INTERVENTIONAL phases: PHASE1 allocation: NA interventionModel: SINGLE_GROUP primaryPurpose: DIAGNOSTIC masking: NONE count: 18 type: ESTIMATED name: Imfinzi name: Opdivo measure: Safety of nivolumab-800CW in combination with durvalumab-680LT measure: To investigate the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo FMI to detect nivolumab-800CW and durvalumab-680LT signals indicating PD1 and PD-L1 expression. measure: Heart rate measure: Blood pressure systolic and diastolic measure: Temperature measure: Determine the PD-1 and PD-L1 expression and the changes in PD-1 and PD-L1 expression before and after nCRT in patients with LARC. measure: Determine the PD-1 and PD-L1 expression and the changes in PD-1 and PD-L1 expression before and after nCRT in patients with LARC. measure: Quantify in vivo fluorescence signals of nivolumab-800CW and durvalumab-680LT before and after CRT by using MDSFR/SFF spectroscopy/UNSB/SFF spectroscopy and correlate these measurements to, in vivo fluorescence intensities and PD1/PD-L1 expression measure: Quantify in vivo fluorescence signals of nivolumab-800CW and durvalumab-680LT before and after CRT by using MDSFR/SFF spectroscopy/UNSB/SFF spectroscopy and correlate these measurements to, in vivo fluorescence intensities and PD1/PD-L1 expression measure: Perform real-time polymerase chain reaction (qPCR) and western blot on biopsies to determine whether there is genetic downregulation or protein degradation of PD-1 and PD-L1 after chemoradiotherapy measure: Compare immune cell composition between the radiated and non-radiated area of the bowel. measure: Evaluate targeted detection with nivolumab-800CW and durvalumab-680LT of the tumor by ex vivo visualization of the resection specimen with PEARL Trilogy sex: ALL minimumAge: 18 Years stdAges: ADULT stdAges: OLDER_ADULT facility: University Medical Center Groningen city: Groningen zip: 9713 GZ country: Netherlands name: Wouter B Nagengast, Prof. role: CONTACT email: w.b.nagengast@umcg.nl name: Lisanne E van Heijst, Bsc. role: SUB_INVESTIGATOR name: Pia Volkmer, Drs. role: SUB_INVESTIGATOR lat: 53.21917 lon: 6.56667 hasResults: False