Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05984810 |
| Other study ID # |
P23.018 |
| Secondary ID |
2023-000026-28NL |
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 18, 2024 |
| Est. completion date |
December 2026 |
Study information
| Verified date |
April 2024 |
| Source |
Leiden University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Pancreatic carcinoma has a dismal prognosis at time of diagnosis, due to late onset of
clinical symptoms, patients present with advance disease. Complete surgical resection is the
only potential curative treatment, however only a small percentage is eligible for upfront
total surgical resection due to extension into anatomical related important vascular
structures. Neoadjuvant chemo(radio)therapy has become the standard treatment modality for
non-primary resectable disease (borderline resectable and locally advanced pancreatic cancer
(LAPC)), where subsequent downstaging can make identification of the primary tumor more
challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by
providing real-time visualization of tumors, suspect lymph nodes and vital structures during
surgery. Additional intra-operative feedback could possibly reduce the frequency of positive
resection margins and increase complete removal of locally spread tumor and involved lymph
nodes and could thereby improve patient outcomes as well as overall survival. SGM-101 is a
targeted NIR-fluorophore, with specific binding capacity for Carcino Embryonic Antigen (CEA)
which is overexpressed on tumor cells in the gastro-intestinal tract, including pancreatic
cancer.
Description:
Pancreatic cancer is a lethal cancer type and is continuously rising as cause of
cancer-related death in the Western World. Despite advances in surgical and systemic
treatment, the 5-year overall survival (OS) rate remains approximately 10%. This low survival
rate is mostly caused by late detection of disease due to the late onset of symptoms.
Therefore, most patients are diagnosed with advanced stage disease: at the time of diagnosis,
about 15% of patients has (borderline) resectable ((B)RPC) disease (stage I or II), 35%
locally advanced pancreatic cancer (LAPC, stage III), and 50% metastatic disease (stage IV).
The resectability of disease is determined by the extent of tumor contact with the superior
mesenteric artery, celiac artery, superior mesenteric vein, and portal vein.
Over the last decade, preoperative chemo(radio)therapy has increasingly been used in an
attempt to downstage BRPC or LAPC and select patients with more favorable tumor biology for
resection, with the aim to reduce the chance for (early) recurrence. In essence, only
patients showing regression or stable disease without suspected metastatic disease are
considered for surgical exploration. However, preoperative therapy complicates the
preoperative radiological staging, because conventional imaging modalities cannot
differentiate between vital tumor tissue, inflammation and fibrosis induced by the
preoperative chemo(radio)therapy. As a consequence, vascular tumor involvement is often
overestimated and also hard to interpret with substantial interobserver variability.
Therefore, non-progressive disease following preoperative therapy regarding imaging and tumor
markers is usually an indication for surgical exploration to determine whether radical
resection is achievable.
During surgical exploration preceding intended tumor resection, the surgeon has to assess the
extent of local (vascular) tumor involvement based on preoperative imaging and visual and
tactile senses. This visual intraoperative White Light Inspection (WLI) combined with tactile
feedback, are the main instruments for guidance and decision-making available to surgeons
nowadays. As a result of neoadjuvant therapy the appearance, dimensions, and tactile feedback
of the target lesion can be altered, mostly as a result of therapy-induced fibrosis, which
complicates the assessment of (local) invasiveness. Surgeons benefit from additional tools
that give them real-time directional feedback on local tumor status, which is one of the
strengths of optical molecular imaging techniques, like Near-infrared fluorescence (NIRF)
imaging. Near-infrared fluorescence (NIRF) imaging is an emerging important intraoperative
tool for enhancement of visual contrast and is able to provide real-time guidance in tumor
visualization and demarcation. Particularly the use of tumor-specific markers coupled to
fluorescent imaging moieties show great promise to improve intraoperative staging and allow
more radical cytoreductive surgery if considered resectable.
The compound that will be studied in this trial is SGM-101, a CEA-specific chimeric antibody
conjugated with a NIR emitting moiety developed by SurgiMab (Montpellier, France). Anti-CEA
monoclonal antibodies have been used in more than 100 clinical studies without any toxicity
concerns. In addition, it has been shown that it is possible to link an anti-CEA monoclonal
antibody to a near-infrared (NIR) emitting fluorophore. Carcinoembryonic antigen (CEA) is a
tumor-specific marker that is highly expressed in a number of tumors of epithelial origin
(such as colorectal carcinoma and pancreas carcinoma) while it is minimally expressed in
normal adult tissues. CEA, among others like Carbohydrate Antigen 19-9 (CA 19-9) is used as
diagnostic and prognostic marker during different stages of malignant pancreatic disease.
From a previous study conducted in the LUMC with this compound in patients with (borderline)
resectable pancreatic cancer the investigators learned that near-infrared fluorescence
imaging of pancreatic tumors using a single dose up to 10mg of the anti-CEA targeted
fluorophore SGM-101 is safe, well-tolerated, feasible and effective. It results in specific
accumulation of SGM-101 in CEA-expressing primary tumors, peritoneal and liver metastases,
allowing real-time identification and guidance using intraoperative fluorescence imaging.
Furthermore, CEA expression on the targeted PDAC tissue is expected to be none to minimally
influenced by the neoadjuvant treatment, either FOLFIRINOX or a combination of Gemcitabine
with or without radiotherapy, as described by previous studies. In addition to experience in
pancreatic tumors, there is ample experience from finalized phase-II and ongoing phase-III
studies in patient with colorectal carcinoma. A recent study in colorectal cancer patients
showed that additional malignant lesions were detected and resected using NIR fluorescence
imaging in 6 out of 17 patients (35%). Moreover, an expansion on this study showed no SGM-101
related adverse events up to 15 milligrams in 75 patients. There were no trends or clinically
relevant changes in vital signs, ECGs or laboratory parameters reported. Any changes in the
laboratory results reported in the follow-up moments were related to the surgical procedure.
Best imaging results (according to the tumor to background ratio) were achieved with 10
milligrams injected 3 to 5 days prior to surgery.
This study evaluates the yield of NIR-Fluorescence imaging as additional surgical-tool for
visualization and assessment of local extent and resectability status of neoadjuvant treated
localized pancreatic tumors, local lymph node-involvement as well as potential distant
metastatic disease using a single intravenous dose of 10mg SGM-101.
Main objective: Determination of the performance of SGM-101 as a fluorescent tracer for
NIR-Fluorescence-guidance (FLI) during surgical pancreatic resections after neoadjuvant
therapy for assessment of (local) tumor extent and delineation of the primary tumor, local
lymph nodes and potential distant metastatic disease
Design:
Part A: This is a single-center prospective clinical cohort study in patients with
neoadjuvant treated non-primarily resectable ((borderline) resectable and locally advanced)
pancreatic cancer undergoing scheduled surgical resection. A total of 20 patients will be
prospectively enrolled in this study evaluating the performance of NIR-Fluorescence imaging
as an additional surgical-tool for the visualization and determination of the local extent of
primary tumor, lymph node-involvement and occult hepatic and peritoneal metastatic disease in
patients using a single dose of 10mg of SGM-101. The selected dose is based on the
pre-clinical and phase I/II results in patients with pancreatic and colorectal cancer.
Part B: Part B is synchronous to part A, to compare and match the TdEV containing blood
samples from patients participating in part A this trial needs 20 healthy donor control blood
samples of 30mL to address our exploratory endpoints regarding TdEV's. Therefore in this
trial 20 healthy volunteers will be asked to participate as anonymous healthy blood donor of
30mL (3 EDTA tubes) peripheral venous blood for a single visit to donate healthy donor blood.
The control samples will be used anonymous and there is no further follow-up or additional
study related activities.
Investigational drug: The Investigational Medicinal Product (IMP) used in part A is the
injectable conjugate SGM-101 is composed of a chimeric monoclonal antibody specific of CEA,
bound to a fluorochrome. SGM-101 is manufactured in compliance with Good Manufacturing
Practice (GMP). It is a sterile solution for injection supplied in 4 mL amber glass vial (5
mg/mL; 2,3 mL/vial). A dose of 10 mg SGM-101 will be administered intravenously over 30
minutes 3 to 5 (±4) days prior to surgery.
Imaging system: The Investigational Medical Device (IMD) used in part A is the imaging system
that will be used in the study is a dedicated NIRF-camera system from Quest Medical Imaging
(Quest Medical Imaging, Olympus Europe) the Quest Spectrum 2/3.0 Platform, that is optimized
for measurements in the 700-800nm NIR-spectrum. For this device ample handling-experience for
end-users exists at the LUMC, gained from standard-of-care and research activities with
intra-operative NIRF-imaging.
