Focus Green: Fluorescence-guided resection Of Colorectal liver metastases Using SGM-101 and Indocyanine GREEN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leiden University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Diseases [C] - Neoplasms [C04]

Trial duration

12 Dec 2023 → 14 May 2025

Decision date (initial)

2023-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis

To assess the feasibility of simultaneous use of ICG and SGM-101 for intraoperative imaging of colorectal liver metastases.

Secondary objectives 10

1. To assess the accuracy of ICG, SGM-101 or both to demonstrate an irradical resection per lesion and per patient level.
2. To assess the in vivo and ex vivo concordance rate of ICG, SGM-101 or both to histopathological status of the resected lesions (benign/malignant), ultimately to diminish the amount of false positive resected lesions
3. To determine the in vivo and ex vivo signal-to-background ratios (SBR) for SGM-101 and ICG;
4. To assess the number of intraoperative changes in surgical plan based on fluorescence (ICG, SGM-101 or both) and correlate this to histopathological status of the resected tissue. These changes comprise of a. Performing an extra resection because of i. An additional fluorescent lesion ii. Suspected fluorescent irradicality b. Preservation of tissue
5. To determine the surgeon’s satisfaction and judged potency (Survey C) on working with SGM-101 in addition to ICG
6. To determine the correlation between fluorescent intensity and tissue CEA expression
7. To determine the effect of tumour depth on fluorescent signal for both ICG and SGM-101
8. To evaluate the feasibility of minimally invasive diagnostic approach for the early detection of colorectal cancer through circulating tumor cells and extracellular vesicles
9. To evaluate the feasibility of using CTCs and EVs in the blood of CRC patients as biomarkers for early detection of recurrence/metastasis
10. To evaluate the feasibility of using CTCs and EVs from peripheral blood for disease monitoring and early cancer detection.

Conditions and MedDRA coding

colorectal livermetastases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Diagnosed with liver metastases of colorectal origin for which surgical resection is proposed and meet at least one of the following criteria: a. Scheduled for surgical resection of >3 CRLM or; b. completed neo-adjuvant therapy, of which the last course was completed within 3 months before surgery or; c. Scheduled for surgery because of a locally recurrent liver metastasis.
2. ≥18 years old.
3. Willing and capable to give informed consent before study specific procedures

Exclusion criteria 3

1. Patients with contraindications for SGM-101 a. History of any anaphylactic shock; b. Patients pregnant or breastfeeding (pregnancy should be ruled out by a pregnancy test within two weeks prior to administration of the conjugate); c. Known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG) or hepatitis C virus (HCV) antibody or patients with untreated serious infections; d. Previous administration of SGM-101
2. Patients with contraindications for Indocyanine green: a. Allergy for shells and/or clamps b. Hyperthyroidism c. Known allergy for ICG
3. Any condition that the investigator considers to be potentially jeopardizing the patient’s well-being or the study objectives

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. A positive score on practical workability measured with survey A ‘practical workability during surgery’ (see section 8.1.4), defined as an average score of at least neutral.
2. A positive score on the patient’s experience measured with survey B ‘patient experience’ (see section 8.1.4), defined as an average score of at least neutral.
3. SGM-101: at least 80% sensitivity, measured as follows: - Capsular lesions, that are visible in white light are only counted positive if TBR ≥ 1.5 in vivo. - Subcapsular lesions that are not visible in white light will be counted as positive if: A: TBR ≥ 1.5 in vivo, OR B: TBR ≥ 1.5 ex vivo on whole specimen OR C: TBR ≥ 1.5 ex vivo on bread loafs
4. No cross-interference of fluorescent signal of both dyes within the two different excitation and emission channels. Cross-Interference is deemed insignificant if at macroscopic bread loaf imaging with the Quest spectrum System: A: At the 800nm channel the rim signal (ICG, 800nm) to tumour (possibly due to SGM-101, 700nm) ratio (STR) ≥ 1.5 in ICG positive tumours. B: At the 700nm channel the tumour (SGM, 700nm) to rim signal (ICG, 800nm) ratio (TRR) ≥ 1.5 in SGM-101 positive tumours

Secondary endpoints 10

1. The accuracy of ICG, SGM-101 or both to demonstrate an irradical resection. The accuracy comprises of the rate of true positives, true negatives, false positives and false negative with accompanied sensitivity, specificity, positive predictive value and negative predictive value
2. Concordance rate of ICG, SGM-101, ICG and SGM-101 combined (both fluorescent) or ICG and SGM-101 combined (for which only one is fluorescent), to histopathological result (lesion benign vs malignant). The concordance rate comprises of the rate of true positives, true negatives, false positives and false negative with accompanied sensitivity, specificity, positive predictive value and negative predictive value.
3. For every lesion a TBR (SGM-101) /SBR (ICG) will be calculated in vivo (Quest open camera), ex vivo whole specimen (Quest open camera, Pearl system) and ex vivo bread loafs (Quest open camera, Pearl system).
4. Modification of operative plan due to imaging (e.g. extension of resection margins, additional resection, preservation of tissue) and the correlation to histopathology.
5. Survey C ‘surgeon’s satisfaction and judged potency’ questionnaire (see section 8.1.4) will be handed to all the surgeons at the end of the trial that have at minimum operated 3 times within this trial. Outcomes will be analysed.
6. To assess the correlation between lesion CEA expression, performed using immunohistochemistry staining, to bread loaf TBR (SGM-101) measured with the Pearl system.
7. Effect of tumour depth on fluorescent status of ICG/SGM-101
8. To evaluate the feasibility of minimally invasive diagnostic approach for the early detection of colorectal cancer through circulating tumor cells and extracellular vesicles.
9. To evaluate the feasibility of using CTCs and EVs in the blood of CRC patients as biomarkers for early detection of recurrence/metastasis.
10. To evaluate the feasibility of using CTCs and EVs from peripheral blood for disease monitoring and early cancer detection.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leiden University Medical Center

Sponsor organisation

Leiden University Medical Center

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leiden University Medical Center

Contact name

Mats Warmerdam

Public contact point

Organisation

Leiden University Medical Center

Contact name

Mats Warmerdam

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications