Fluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery in Locally Advanced Rectal Cancer

NCT ID: NCT04638036

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-13
• Study Completion Date: 2023-05-21

Brief Summary

Treatment of patients with locally advanced rectal cancer (LARC) is multidisciplinary and consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgical removal of the rectal tumor and potentially tumor positive lymph nodes.

1. After surgery, in 15 to 27% of patients that received nCRT no tumor cells can be detected during histopathological examination. In today's clinical practice, all of these patients with a pathological complete response (pCR) are operated upon, with substantial morbidity and mortality. The 5-year survival is 83.3% for patients with a pCR, and 65.6% for those without pCR. Response after nCRT is currently evaluated using magnetic resonance imaging (MRI). However, as MRI cannot differentiate between molecular characteristics of tissue, prediction of treatment response can be inaccurate. In patients with a potential cCR on MRI, additionally a high-definition white-light (HD-WL) endoscopy is performed with biopsies of the previous tumor location. If both MRI and HD-WL endoscopy confirm a potential cCR, patients can also be treated with a watch-and-wait approach, including frequent follow-up with HD-WL endoscopy and MRI. This potentially prevents extensive surgical procedures for patients in which this is not required. However, MRI and HD-WL endoscopy often remain insufficient for identification of cCR. Therefore, novel imaging methods are needed for accurate prediction of treatment response in order to select patients. The investigators believe fluorescence molecular endoscopy (FME) could be a promising technique for evaluation of treatment response.

2. During surgery, tumor-negative resection margins are of great prognostic value. Currently, surgeons rely on visual and tactile inspection for differentiation between malignant and healthy tissue. When in doubt, a frozen section can be obtained, which is time consuming and poses a high risk of sampling error. However, 14.7% of patients still have tumor-positive resection margins, increasing the risk of local recurrence and worsening outcome. Therefore, there is a need for novel imaging techniques that can be used intraoperatively to improve margin assessment. The investigators believe molecular fluorescence-guided surgery (MFGS) could be a promising technique for evaluation of resection margins.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

NIR endoscopy and surgery with cetuximab-IRDye800CW

In this non-randomized, non-blinded, prospective, feasibility study, cetuximab-IRDye800CW will be administered to a total of 15 patients with proven locally advanced rectal cancer

Group Type: EXPERIMENTAL

Cetuximab-IRDye800

Intervention Type: DRUG

Intravenous administration of a pre-dose of 75 mg unlabeled Cetuximab followed by 15 mg Cetuximab-IRDye800 prior to the study procedures

Fluorescent molecular endoscopy and surgery

Intervention Type: DEVICE

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe can be inserted through the standard working channel of the standard clinical endoscope for fluorescent endoscopy. Fluorescence imaging will be performed post the chemoradiotherapy.

Interventions

Cetuximab-IRDye800

Intravenous administration of a pre-dose of 75 mg unlabeled Cetuximab followed by 15 mg Cetuximab-IRDye800 prior to the study procedures

Intervention Type: DRUG

Fluorescent molecular endoscopy and surgery

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe can be inserted through the standard working channel of the standard clinical endoscope for fluorescent endoscopy. Fluorescence imaging will be performed post the chemoradiotherapy.

Intervention Type: DEVICE

Other Intervention Names

Tracer administration

Eligibility Criteria

Inclusion Criteria

• Locally advanced rectal cancer, in multi-disciplinary colorectal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by surgical removal of the primary tumor;
• Clinical suspicion of residual tumor after neoadjuvant chemoradiotherapy;
• 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;
• Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
• Received an investigational drug within 30 days prior to the dose of cetuximab- IRDye800CW;
• History of infusion reactions to cetuximab or other monoclonal antibodies;
• Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina pectoris;
• Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents;
• Evidence of QT prolongation on an ECG made within three months prior to inclusion (greater than 440 ms in males or greater than 450 ms in females);
• Magnesium, potassium and calcium deviations that might lead to cardiac rhythm (grade II or higher deviations by CTCAE), determined within three months prior to inclusion.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

Other Identifiers

NL61406.042.17

Identifier Type: -

Identifier Source: org_study_id