Quantitative Fluorescence Endoscopy Using Durvalumab-680LT in Esophageal Cancer

Sponsor
University Medical Center Groningen
Study ID
NCT05450484
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Fluorescence endoscopy using durvalumab-680LT — DRUG
    Tracer administration: The PD-L1-targeted fluorescent tracer durvalumab-680LT will be administered intravenously 2-4 days prior to the endoscopy at the UMCG. Afterwards, patients will be monitored for half an hour by measurements of vital parameters for potential side-effects, such as infusion-related reactions. Endoscopy procedure: Patients will undergo two endoscopies, before and after neoadjuvant therapy. First, routine high-definition white-light (HD-WL) inspection is used. Quantification of fluorescence using multi-diameter single fiber reflectance/single fiber fluorescence (MDSFR/SFF) spectroscopy will be performed both in vivo and ex vivo. Subsequently, fluorescence molecular endoscopy (FME) and endoscopic ultrasound (EUS) will be performed. EUS enables single fiber reflectance/single fiber fluorescence (SFR/SFF) spectroscopy measurements via fine needle aspiration (FNA) to gain insight in the drug distribution throughout the tumor. Additionally, biopsies will be obtained.

Study Details

Treatment of patients with locally advanced esophageal cancer (EC) is multidisciplinary and consists of neoadjuvant therapy followed by surgical removal of the esophageal tumor and potentially tumor positive lymph nodes. The beneficial effect of the addition of immunotherapy to improve response rates to current treatment strategies has been investigated response to, since only 16 to 43% of EC patients achieve a pathological complete response (pCR) after neoadjuvant therapy and a pCR is associated with better long-term outcomes. Unfortunately, not all patients respond to immunotherapy and the knowledge about biomarkers that predict response to therapy are required. A promising novel parameter is tumor programmed death-ligand 1 (PD-L1) expression, one of the immune checkpoints targeted by cancer immunotherapy. Studies performed in patients with various solid tumors demonstrate improved response to immunotherapy and survival benefit in patients with higher PD-L1 expression. Nonetheless, not all patients with high PD-L1 expression show benefit and some without expression do. Moreover, mostly biopsy-based tests are used to assess PD-L1 status, although these tests are prone to errors, partly due to heterogeneity in tissue expression. Novel methods are needed to gain more insight in the PD-L1 expression in order to better select patients who are likely to benefit from immunotherapy. The investigators hypothesize that quantitative fluorescence endoscopy using the tracer durvalumab-680LT targeting PD-L1 is a promising technique to investigate the heterogeneity of PD-L1 expression.

Key Dates

Start date
Apr 5, 2023
Status verified
Apr 2026
Primary completion
Nov 25, 2024
Completion
Dec 1, 2024

Study Design

Enrollment
21 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC

Arms

  • Experimental: Durvalumab-680LT

Primary Outcome Measure

1) Evaluating the heterogeneity of the PD-L1 tumor expression before and after neoadjuvant therapy using quantitative fluorescence endoscopy using the PD-L1-targeted fluorescent tracer durvalumab-680LT [ Time Frame: Within 12 months after the study procedures ]

Related Studies