1. To assess safety of different doses of a single iv injection of SGM-1012. To assess the performance of SGM-101 in the intraoperative detection of colorectal or pancreas cancer by:a. Tumor-to-background ratio (TBR);b. Concordance between…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability (primary endpoint)
Tolerability/safety will be assessed using routine clinical measures such
treatment-emergent adverse events, blood pressure, heart rate, temperature,
peripheral oxygen saturation, respiratory rate, skin examination, and routine
laboratory assessments.
Secondary outcome
Performance (secondary endpoint)
Performance of SGM-101 will be defined by tumor to background ratio (TBR) for
fluorescence, and the concordance between the intraoperative fluorescence
assessment of suspected lesions and their histopathology. In addition after
resection, margins will be assessed using fluorescence imaging to detect
potential irradical resection.
Pharmacokinetics (secondary endpoint)
Cmax, T*, AUC, Tmax, Clearance. In addition, the relationship between
pharmacokinetics and performance will be assessed.
Background summary
Surgery is the most important therapy for patients with cancer of the colon,
rectum or pancreas. Complete resection, which is a crucial factor in the
prognosis of a patient, is challenging as surgeons have to rely on visual
appearance and palpation to discriminate between tumor and normal tissue.
Consequently, incomplete resection of malignant tissue or unnecessary removal
of healthy tissue may occur. This problem may become bigger as *open* surgery
is increasingly replaced by *closed* (laparoscopic) surgery. It is therefore
that real-time intra-operative imaging techniques are developed. 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.
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. 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. The compound that will be studied in this research
project is SGM-101, a CEA-specific chimeric antibody conjugated with a NIR
emitting moiety developed by SurgiMab (Montpellier, France). The hypothesis is
that, following preoperative iv administration of SGM-101 in patients with
carcinoma of the rectum or pancreas, SGM-101 will bind to CEA expressing cancer
cells and these cells can then be visualized with a NIR fluorescence imaging
system, thereby increasing the chance of radical resection.
As the experience with SGM-101 in humans is limited, an escalating dose design
will be used which allows assessment of safety and will yield data on the most
appropriate dose to be used in subsequent clinical studies.
Study objective
1. To assess safety of different doses of a single iv injection of SGM-101
2. To assess the performance of SGM-101 in the intraoperative detection of
colorectal or pancreas cancer by:
a. Tumor-to-background ratio (TBR);
b. Concordance between fluorescent signal and tumor status of resected tissue;
c. Concordance between fluorescent signal and tumor status of resection
margins.
3. To assess the pharmacokinetics of ascending doses of a single i.v. injection
of SGM-101
4. To define the optimal dose of SGM-101 for intraoperative imaging of colon,
rectum and pancreas cancer
Study design
Open-label, single ascending dose (range 5-15mg), exploratory study in cohorts
of 6 patients (3 pancreas cancer/ 3 colorectal cancer).
Study burden and risks
The risks of participation for the patients in the trial include
hypersensitivity reactions. These risks are deemed minimal. Nevertheless
precautionary measures (supervised administration by qualified staff and
availability of medical treatment to treat hypersensitivity reactions) are in
place and these effects are generally well manageable. The burden of the trial
is minimal, the research will for the largest
part coincide with routine care and the proposed procedures are minimally
invasive. We therefore believe this research that, could possibly provide a
useful tool to reduce positive resection margins hence reducing rates of
re-interventions and increase the identification rate of otherwise occult
malignant lesions and possibly improves patient outcome and may be used in
staging procedures, is justified.
avenue Henri Becquerel 1025
Montpellier 34000
FR
avenue Henri Becquerel 1025
Montpellier 34000
FR
Listed location countries
Age
Inclusion criteria
1. Patients aged over 18 years old;
2. Patient should be scheduled and eligible for surgery because of a clinical diagnosis of cancer of the colon rectum or cancer of the pancreas;
3. Both pancreatic and colorectal cancer patients: Circulating plasma CEA * the upper limit of normal range (eg * 3.0 ng / ml);
Patient suffering from recurrences and metastasis of colorectal cancer: Rising circulating plasma CEA);
4. Patients should be capable and willing to give informed consent before study specific procedures.
Exclusion criteria
1. Anticancer therapy (e.g. chemotherapy, radiotherapy (except for routine pre-operative radiotherapy in rectal cancer), targeted therapy, concomitant systemic immune therapy, or any experimental therapy) within 4 weeks before inclusion;
2. History of a clinically significant allergy;
3. Circulating plasma concentration CEA * 300 ng / ml;
4. Other malignancies either currently active or diagnosed in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma;
5. Patients pregnant or breastfeeding (pregnancy should be ruled out by an assay of *hCG plasma within two weeks prior to administration of the conjugate), lack of effective contraception in male or female patients with reproductive potential;
6. Laboratory abnormalities defined as:
Rectal cancer patients only:
* Aspartate AminoTransferase, Alanine AminoTransferase, Gamma Glutamyl Transferase) or Alkaline Phosphatase levels above 5 times the or;
* Total bilirubin above 2 times the ULN or;
Both pancreatic and colorectal cancer patients:
* Serum creatinine above 1.5 times the ULN or;
* Absolute neutrophils counts below 1.5 x 109/L or;
* Platelet count below 100 x 109/L or;
* Hemoglobin below 4 mmol/L (females) or below 5 mmol/l (males).
7. 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;
8. Any condition that the investigator considers to be potentially jeopardizing the patients well-being or the study objectives.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003281-88-NL |
| CCMO | NL54512.056.15 |
| OMON | NL-OMON21037 |