SGM-101 Tumor Targeted Fluorescence Endoscopy in Rectal Polyps With Suspected T1 Adenocarcinoma or High Grade Dysplasia

NCT ID: NCT06280690

Last Updated: 2024-02-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2025-07-30

Brief Summary

This will be the first trial investigating whether tumor targeted fluorescence is able to discriminate invasive T1 carcinoma / High grade dysplasia from Low grade dysplasia/normal tissue during endoscopic intraluminal resection. This will be done using the CEA-targeted fluorescent probe SGM-101.

Detailed Description

Selection of patients with early rectal cancer, T1 rectal cancer (T1RC) or high-grade dysplasia (HGD), for local resection is based on endoscopic imaging, endorectal ultrasound and/or MRI. However, all these imaging modalities have their limitations in the accurate detection of small areas of cancer in large rectal polyps. Fluorescent guided endoscopy may offer the opportunity to aid in detecting these small cancerous areas in colorectal polyps.

Detection of T1RC or HGD in large rectal polyps is essential to select patients for the appropriate (endoscopic) resection technique. Completely benign polyps, solely containing low-grade dysplasia (LGD), could be resected by piecemeal endoscopic mucosal resection (pEMR), a fast technique on which almost all endoscopists are trained. However, for rectal polyps with T1RC or HGD, curative resection must be achieved by en-bloc resection techniques such as endoscopic submucosal dissection (ESD) or endoscopic intermuscular dissection (EID). These techniques are more complex and expensive and only a small number of endoscopists are trained on these techniques. pEMR of lesions with HGD or T1RC must be avoided because they may result in irradical resections (R1) or in inconclusive histological margin assessment since the polyp is not resected en-bloc. Often, this leads to unnecessary additional abdominal surgical resections.

Furthermore reported sensitivities for optical diagnosis of T1RC in a polyp are low, varying from 20.8% to 77.8%. Because of the limited accuracy of optical diagnosis, the current Dutch guideline suggest that rectal polyps >3cm should be resected in an en-bloc manner, although it has been demonstrated that only 10.2% of rectal polyps >3cm contain a malignant component. Similarly, in recent studies it was shown that 10-15% of entirely benign polyps were removed by abdominal surgery rather than endoscopically. This has major implications for the patient since surgical resection is associated with considerable morbidity. Therefore, there is a need of a technique that provide the endoscopist with real-time information about specific molecular features of the tumor to differentiate between benign polyps with LGD amenable for pEMR and those that contain HGD or T1RC that require en-bloc resection. Tumor targeted fluorescence-guided surgery (FGS) has emerged as a technique with the potential to enable real-time lesion visualization based on specific molecular features rather than on morphology. Recently it was shown that carcinoembryonic antigen (CEA) is overexpressed in approximately 75% of T1RC/HGD. Additionally, expression in LGD was (nearly) absent in 66% of low-grade dysplastic tissue and in 98% of normal rectum tissue, making it a suitable marker for distinguishing T1RC and HGD from LGD and normal tissue. CEA can be targeted by SGM-101, an anti-CEA antibody attached to a fluorophore which has been studied in several clinical studies for patients with colorectal cancer undergoing surgery. The investigators hypothesize that the use of SGM-101 during endoscopy aids the endoscopist in discriminating benign polyps with solely LGD from polyps containing T1RC/HGD.

Conditions

Colorectal Cancer; Image; Low Grade Dysplasia of Colon

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

10mg SGM-101

This cohort receives 10mg

Group Type: EXPERIMENTAL

SGM-101

Intervention Type: DRUG

SGM-101 is cea-targeted fluorescent dye

5mg SGM-101

This cohort receives 5mg

Group Type: EXPERIMENTAL

SGM-101

Intervention Type: DRUG

SGM-101 is cea-targeted fluorescent dye

Interventions

SGM-101

SGM-101 is cea-targeted fluorescent dye

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient must have suspected T1RC/HGD and scheduled for a local endoscopic en-bloc resection. The rectum is defined as the area between the linea dentata and 10cm ab ano.

2. Age > 18 years old

3. Patients should be capable and willing to give signed informed consent before study specific procedures.

Exclusion Criteria

1. Prior participation in this study

2. Previous administration of SGM-101

3. Patients with a history of anaphylactic shock

4. Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential

5. Any condition that the investigator considers to be potentially jeopardizing the patients' well-being or the study objectives.

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

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Alexander Vahrmeijer

Dr. A.L. Vahrmeijer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Leiden University Medical Center

Leiden, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Mats Warmerdam, Msc

Role: CONTACT

m.i.warmerdam@lumc.nl

+31715298420

Facility Contacts

Mats Warmerdam, Msc

Role: primary

m.i.warmerdam@lumc.nl

+31715298420

Other Identifiers

NL83765.058.23

Identifier Type: -

Identifier Source: org_study_id