Fluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery in Locally Advanced Rectal Cancer (TRACT-II)

• ClinicalTrials.gov Identifier: NCT04638036
• Recruitment Status: Unknown
• First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Sponsor: University Medical Center Groningen
• Information provided by (Responsible Party): dr. W.B. Nagengast, MD, University Medical Center Groningen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rectal Cancer	Drug: Cetuximab-IRDye800; Device: Fluorescent molecular endoscopy and surgery	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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
• Actual Study Start Date: November 13, 2020
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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

Drug: Cetuximab-IRDye800; Intravenous administration of a pre-dose of 75 mg unlabeled Cetuximab followed by 15 mg Cetuximab-IRDye800 prior to the study procedures; Other Name: Tracer administration; Device: 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.

Outcome Measures

Primary Outcome Measures :

1. Safety of molecular fluorescence endoscopy using Cetuximab-800CW [ Time Frame: up to 3 months ]
   Number of participants with treatment-related (serious) adverse events
2. Safety of molecular fluorescence-guided surgery using Cetuximab-800CW [ Time Frame: up to 3 months ]
   Number of participants with treatment-related (serious) adverse events
3. Feasibility of molecular fluorescence endoscopy using Cetuximab-800CW [ Time Frame: up to 3 months ]
   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.
4. Feasibility of molecular fluorescence-guided surgery using Cetuximab-800CW [ Time Frame: up to 3 months ]
   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.

Secondary Outcome Measures :

1. Quantifcation of the fluorescent signals [ Time Frame: up to 3 months ]
   To quantify fluorescence signals in vivo and ex vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements
2. Correlation of the fluorescent signal to histopathology and immunohistochemistry [ Time Frame: up to 3 months ]
   To correlate and validate fluorescence signals detected in vivo with ex vivo histopathology and immunohistochemistry
3. Evaluation of the distribution of Cetuximab-IRDye800CW [ Time Frame: up to 3 months ]
   To evaluate the distribution of cetuximab-IRDye800CW on a microscopic level using fluorescence microscopy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: W.B. Nagengast, MD, PhD, PharmD; +31503612620; w.b.nagengast@umcg.nl

Contact: A.M. van der Waaij, MD; +316 - 25647650; a.m.van.der.waaij@umcg.nl

Locations

Netherlands

University Medical Center Groningen; Recruiting

Groningen, Netherlands, 9713 GZ

Contact: W.B. Nagengast, MD, PhD, PharmD +31503612620 w.b.nagengast@umcg.nl

Contact: A.M. van der Waaij, MD +316 - 25647650 a.m.van.der.waaij@umcg.nl

Sponsors and Collaborators

University Medical Center Groningen

More Information

• Responsible Party: dr. W.B. Nagengast, MD, Prof. Dr. W.B. Nagengast, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT04638036
• Other Study ID Numbers: NL61406.042.17
• First Posted: November 20, 2020
• Last Update Posted: November 20, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Rectal Neoplasms; Rectal Diseases; Cetuximab; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Antineoplastic Agents, Immunological; Antineoplastic Agents