Real-time Targeted Fluorescence Endoscopy for Detection of the Primary Cancer Lesion in Patients With a Metastasis of Unknown Primary Tumor in the Head and Neck (REFLECT)

In current diagnostic work-up of patients with a cancer of unknown primary (CUP), approximately 50% of the primary tumor lesions remains undetected. Identification of the primary tumor site results in minimizing the potential morbidity from treatment by reducing morbidity by omitting the need for a mucosectomy of the bilateral base of tongue and tonsils, reducing the radiation field and better oncologic outcome than those with unidentified primary tumor. Clearly, new endoscopic 'real-time' imaging techniques are needed to visualize mucosal changes associated with head and neck squamous cell carcinoma and increase detection rate of the primary tumor. Targeted fluorescence endoscopy enables the visualization of targeted tumor-specific biomarkers by using fluorescence, thereby enhancing the contrast between normal mucosa and tumor tissue. This could improve the detection of the primary tumor in cases where the primary tumor is not detected with white light endoscopy.

Study Overview

• Status: Recruiting
• Conditions: Oropharynx Cancer; Unknown Primary Tumors
• Intervention / Treatment: Diagnostic test: Detection of lesions using fluorescence molecular imaging

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Max JH Witjes, MD, PhD; Phone Number: +31-50-3616161; Email: m.j.h.witjes@umcg.nl
    • Contact: Floris J Voskuil, MD, PhD; Phone Number: +31-50-3616161; Email: f.j.voskuil@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cytology and/or histology-confirmed diagnosis of squamous cell carcinoma most likely originating from the head & neck area and scheduled to undergo endoscopy of the upper aerodigestive tract as decided by the multidisciplinary head and neck tumor board of the UMCG;
• The primary tumor was not identified during standard diagnostic work-up in the outpatient clinic including physical head and neck examination, fiberoptic laryngoscopy, chest X-ray, CT and PET/CT;
• Age ≥ 18 years;
• Written informed consent;

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent;
• Concurrent uncontrolled medical conditions;
• Received an investigational drug within 30 days prior to the dose of cetuximab-800CW;
• History of myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease (ALT >3X upper limits of normal or increased total bilirubin) or unstable angina within 6 months prior to enrollment;
• Inadequately controlled hypertension with or without current antihypertensive medications;
• History of allergy or infusion reactions cetuximab or other monoclonal antibody therapies;
• Pregnant or lactating women. Documentation of a negative pregnancy test must be available for women of childbearing potential. Moreover, the need to be willing to ensure that she or her partner uses effective contraception during the trial and for 6 months thereafter. Woman of childbearing potential are premenopausal women with intact reproductive organs and women less than two years after menopause;
• Evidence of QT prolongation on pretreatment ECG (greater than 440 ms in males or greater than 450 ms in females)
• Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
• Life expectancy < 12 weeks;
• Karnofsky performance status < 70%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; Patients with cancer of unknown primary most probable originating from the head and neck area	Diagnostic test: Detection of lesions using fluorescence molecular imaging; Using a fluorescence camera, lesions will be detected and biopsies will be taken to try and find cancer of unknown primary

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy in detecting primary tumours compared to white light endoscopy.	To determine the feasibility of targeted fluorescence endoscopy compared to white light endoscopy and a mucosectomy using cetuximab-800CW for the detection of the primary tumor in patients with CUP	During surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety aspects of cetuximab-800CW	To obtain information on safety aspects of cetuximab-800CW administration by registration of side effects, adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR);	through study completion
Accuracy in detecting primary tumours with flexible fluorescence laryngoscopy at the outpatient clinic for primary tumor detection rates	Accuracy in detecting primary tumours with flexible fluorescence laryngoscopy at the outpatient clinic for primary tumor detection rates	Flexible endoscopy will be performed 1-0 days before surgery.
To quantify intrinsic fluorescence signals of cetuximab-800CW;	To quantify intrinsic fluorescence signals of cetuximab-800CW;	During the procedure
To determine if ex vivo fluorescence imaging using cetuximab-800CW can be used for assessment of the surgical specimen after mucosectomy;	To determine if ex vivo fluorescence imaging using cetuximab-800CW can be used for assessment of the surgical specimen after mucosectomy;	immediatly after the procedure
To determine the specificity and positive predictive value of TFE and WLE for the detection of the primary tumor in patients with CUP.	To determine the specificity and positive predictive value of TFE and WLE for the detection of the primary tumor in patients with CUP.	end of study
To correlate and validate fluorescence signals in vivo and ex vivo with histopathology.	To correlate and validate fluorescence signals in vivo and ex vivo with histopathology.	1-2 weeks after procedure
To study health-related quality of life data regarding the standard of care mucosectomy procedures performed with transoral robot surgery using the QLQ-C30, QLQH&N35 en de SWAL-QoL.	To study health-related quality of life data regarding the standard of care mucosectomy procedures performed with transoral robot surgery.	up to 6 weeks after surgery

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Unknown Primary; Oropharyngeal Neoplasms
• Other Study ID Numbers: 10949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No