protocolSection identificationModule nctId: NCT06304597, orgStudyIdInfo id: 17651, briefTitle: Evaluating PD-1/PD-L1 in Locally Advanced Rectal Cancer by Quantitative Fluorescence Molecular Endoscopy, acronym: PREDICT, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2025-03-01, completionDateStruct date: 2025-06-01, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: University Medical Center Groningen, class: OTHER, descriptionModule 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., conditionsModule conditions: Locally Advanced Rectal Carcinoma, designModule studyType: INTERVENTIONAL, phases: PHASE1, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: DIAGNOSTIC, maskingInfo masking: NONE, enrollmentInfo count: 18, type: ESTIMATED, armsInterventionsModule interventions name: Imfinzi, interventions name: Opdivo, outcomesModule primaryOutcomes measure: Safety of nivolumab-800CW in combination with durvalumab-680LT, primaryOutcomes 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., primaryOutcomes measure: Heart rate, primaryOutcomes measure: Blood pressure systolic and diastolic, primaryOutcomes measure: Temperature, secondaryOutcomes 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., secondaryOutcomes 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., secondaryOutcomes 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, secondaryOutcomes 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, secondaryOutcomes 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, secondaryOutcomes measure: Compare immune cell composition between the radiated and non-radiated area of the bowel., secondaryOutcomes measure: Evaluate targeted detection with nivolumab-800CW and durvalumab-680LT of the tumor by ex vivo visualization of the resection specimen with PEARL Trilogy, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: University Medical Center Groningen, city: Groningen, zip: 9713 GZ, country: Netherlands, contacts name: Wouter B Nagengast, Prof., role: CONTACT, email: w.b.nagengast@umcg.nl, contacts name: Lisanne E van Heijst, Bsc., role: SUB_INVESTIGATOR, contacts name: Pia Volkmer, Drs., role: SUB_INVESTIGATOR, geoPoint lat: 53.21917, lon: 6.56667, hasResults: False