To hear about similar clinical trials, please enter your email below
Trial Title:
Evaluating PD-1/PD-L1 in Locally Advanced Rectal Cancer by Quantitative Fluorescence Molecular Endoscopy
NCT ID:
NCT06304597
Condition:
Locally Advanced Rectal Carcinoma
Conditions: Official terms:
Rectal Neoplasms
Nivolumab
Durvalumab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Imfinzi
Description:
Durvalumab is labeled to IRDye-680LT and will be administered in combination with
fluorescently labelled nivolumab (Opdivo)
Arm group label:
Durvalumab-680LT and nivolumab-800CW
Other name:
durvalumab
Intervention type:
Drug
Intervention name:
Opdivo
Description:
Nivolumab is labeled to IRDye-800CW and will be administered in combination with
fluorescently labelled durvalumab (Imfinzi)
Arm group label:
Durvalumab-680LT and nivolumab-800CW
Other name:
Nivolumab
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.
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Diagnosed with LARC (cT3c-4, N1-2, M0);
- Written informed consent is obtained; (We aim to include only patients who consent
to both study procedures, however if some patients (n<9) do not consent to the first
or second procedure or withdraw their consent for the second procedure after the
first procedure, they can still be included)
- Be at least 18 years old;
- Speak the Dutch language.
Exclusion Criteria:
- Concurrent uncontrolled medical conditions according to treating medical physician;
- Pregnancy or breast feeding. A negative pregnancy test must be available for women
of childbearing potential on the day of tracer administration (i.e. premenopausal
women with intact reproductive organs and women less than two years after
menopause);
- Prior irradical endoscopic mucosal resection (EMR) or endoscopic submucosal
dissection (ESD) of the primary tumor.
- Received an investigational drug within 30 days prior to administration of
nivolumab-800CW and durvalumab-680LT according to the patient's medical history;
- History of infusion reactions to nivolumab, durvalumab or other monoclonal
antibodies according to the patient's medical history;
- Active episode of inflammatory bowel disease;
- Use of immunosuppressive agents;
- Medical or psychiatric conditions that compromise the patient's ability to give
informed consent according to treating medical physician.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Medical Center Groningen
Address:
City:
Groningen
Zip:
9713 GZ
Country:
Netherlands
Contact:
Last name:
Wouter B Nagengast, Prof.
Email:
w.b.nagengast@umcg.nl
Investigator:
Last name:
Lisanne E van Heijst, Bsc.
Email:
Sub-Investigator
Investigator:
Last name:
Pia Volkmer, Drs.
Email:
Sub-Investigator
Start date:
April 1, 2024
Completion date:
June 1, 2025
Lead sponsor:
Agency:
University Medical Center Groningen
Agency class:
Other
Source:
University Medical Center Groningen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06304597