Clinical trial NCT04638036: Fluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery in Locally Advanced Rectal Cancer
Official title: Fluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery of Locally Advanced Rectal Cancer Using Cetuximab-IRDye800CW: a Single-center Feasibility and Safety Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rectal Cancer
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2020-11-20
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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.

Primary outcomes:
measure: Safety of molecular fluorescence endoscopy using Cetuximab-800CW
timeFrame: up to 3 months
measure: Safety of molecular fluorescence-guided surgery using Cetuximab-800CW
timeFrame: up to 3 months
measure: Feasibility of molecular fluorescence endoscopy using Cetuximab-800CW
timeFrame: up to 3 months
measure: Feasibility of molecular fluorescence-guided surgery using Cetuximab-800CW
timeFrame: up to 3 months
Secondary outcomes:
measure: Quantifcation of the fluorescent signals
timeFrame: up to 3 months
measure: Correlation of the fluorescent signal to histopathology and immunohistochemistry
timeFrame: up to 3 months
measure: Evaluation of the distribution of Cetuximab-IRDye800CW
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References: