Trial Title:
NIR-Fluorescence Guided Surgical Resection of Neoadjuvant Treated Localized Pancreatic Cancer Using SGM-101
NCT ID:
NCT05984810
Condition:
Pancreas Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Conditions: Keywords:
Fluorescence Guided Surgery
Pancreatic Ductal Adenocarcinoma
Neoadjuvant therapy
Near-Infrared (NIR) Fluorescence imaging
CEA
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Fluorescence-guided surgery using CEA-targeted fluorophore SGM-101
Description:
Fluorescence-guided surgery using CEA-targeted fluorophore SGM-101
Arm group label:
10mg, administered 3-5 days before surgery
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.
Detailed 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.
Criteria for eligibility:
Criteria:
INCLUSION CRITERIA
Part A: To be eligible for inclusion in this study, patients must meet all of the
following criteria:
1. Signed informed consent prior to any study-mandated procedure;
2. Patients aged over 18 years old;
3. Has the ability to communicate well with the Investigator in the Dutch/English
language and willing to comply with the study restrictions.
4. Neoadjuvant treated (borderline) resectable or locally advanced pancreatic cancer
scheduled for a surgical resection
Part B: To be eligible for inclusion in this study, healthy volunteers must meet all of
the following criteria:
1. Signed informed consent prior to any study-mandated procedure;
2. Patients aged over 18 years old;
3. Has the ability to communicate well with the Investigator in the Dutch/English
language.
EXCLUSION CRITERIA
Part A: To be eligible for conclusion in this study, patients must meet none of the
following criteria:
1. History of clinically significant anaphylactic reactions;
2. Previous administration of SGM-101;
3. Pregnant women, or women giving breast feeding;
4. Any condition that the investigator considers to be potentially jeopardizing the
patient's well-being or the study objectives.
Part B: To be eligible for conclusion in this study, healthy volunteers must meet none of
the following criteria:
1. Previous administration of SGM-101;
2. Pregnant women, or women giving breast feeding;
3. Any condition that the investigator considers to be potentially jeopardizing the
patient's well-being or the study objectives.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Leiden University Medical Center
Address:
City:
Leiden
Zip:
2300RC
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Alexander Vahrmeijer, MD, PhD
Phone:
0715269111
Email:
a.l.vahrmeijer@lumc.nl
Contact backup:
Last name:
Martijn van Dam, MD
Email:
m.a.van_dam@lumc.nl
Investigator:
Last name:
Alexander Vahrmeijer, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Martijn van Dam, MD
Email:
Sub-Investigator
Investigator:
Last name:
Sven Mieog, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Agustin Enciso-Martinez, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Peter Ten Dijke, PhD
Email:
Sub-Investigator
Start date:
March 18, 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Leiden University Medical Center
Agency class:
Other
Collaborator:
Agency:
Dutch Cancer Society
Agency class:
Other
Collaborator:
Agency:
Surgimab
Agency class:
Industry
Source:
Leiden University Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05984810
