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

NCT04638036 | Completed Phase 1

• 1 other identifier: NL61406.042.17
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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. 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. 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

Outcome Measures

Primary Outcomes (4)

• Safety of molecular fluorescence endoscopy using Cetuximab-800CW

  Number of participants with treatment-related (serious) adverse events

  up to 3 months

• Safety of molecular fluorescence-guided surgery using Cetuximab-800CW

  Number of participants with treatment-related (serious) adverse events

  up to 3 months

• Feasibility of molecular fluorescence endoscopy using Cetuximab-800CW

  Feasibility will be evaluated by assessing real-time during endoscopy whether fluorescence can be visualized and by taking images during fluorescence molecular endoscopy. Thereafter the fluorescence intensity using the raw data will be measured and a tumor-to-background ratio will be calculated.

  up to 3 months

• Feasibility of molecular fluorescence-guided surgery using Cetuximab-800CW

  Feasibility will be evaluated by assessing whether fluorescence can be detected in the resection margins and on the specimen. Thereafter the fluorescence intensity using the raw data will be measured and a tumor-to-background ratio will be calculated.

  up to 3 months

Secondary Outcomes (3)

• Quantifcation of the fluorescent signals

  up to 3 months

• Correlation of the fluorescent signal to histopathology and immunohistochemistry

  up to 3 months

• Evaluation of the distribution of Cetuximab-IRDye800CW

  up to 3 months

Study Arms (1)

NIR endoscopy and surgery with cetuximab-IRDye800CW

EXPERIMENTAL

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

Drug: Cetuximab-IRDye800; Device: Fluorescent molecular endoscopy and surgery

Interventions

Cetuximab-IRDye800 DRUG

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

Also known as: Tracer administration

NIR endoscopy and surgery with cetuximab-IRDye800CW

Fluorescent molecular endoscopy and surgery 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.

NIR endoscopy and surgery with cetuximab-IRDye800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 20, 2020
• Study Start: November 13, 2020
• Primary Completion: January 28, 2022
• Study Completion: May 21, 2023
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

NL (1)