Clinical trial NCT02973672: Phase I of SGM-101 in Patients With Cancer of the Colon, Rectum or Pancreas
Official title: A Phase I Study Assessing the Safety and Performance of SGM-101, a Fluorochrome-labeled Anti-carcino-embryonic Antigen Monoclonal Antibody for the Detection of Neoplastic Lesions in Patients With Colorectal Cancer or Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colon Cancer
Rectum Cancer
Pancreas Cancer
Metastatic Colorectal Cancer
Recurrent Colorectal Carcinoma
Keywords: Fluorescence
Surgery
Cancer
SGM-101
Near Infrared
Immunophotodetection
Lead sponsor: Surgimab
Sponsor class: INDUSTRY
Collaborators: name: Centre for Human Drug Research, Netherlands
name: Leiden University Medical Center
name: Erasmus Medical Center
name: Catharina Ziekenhuis Eindhoven
First posted: 2016-11-25
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This study evaluates the safety and performance of SGM-101, a Carcinoembryonic Antigen (CEA)-specific chimeric antibody conjugated with a NIR emitting fluorochrome, for the visualization of CEA-expressing cancers during surgery. SGM-101 is injected 2 to 4 days before surgery and visualized using an optimized camera system.

Detailed description: 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.

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. The compound that will be studied in this research project is SGM-101, a CEA-specific chimeric antibody conjugated with a near-infrared (NIR) emitting moiety. The hypothesis is that, following preoperative iv administration of SGM-101 in patients with carcinoma of the colon, 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.

Eligibility criteria: Inclusion Criteria:

* Patients aged over 18 years old;
* Patient should be scheduled and eligible for surgery because of a clinical diagnosis of cancer of the colon, rectum or cancer of the pancreas;
* 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
* Patients should be capable and willing to give informed consent before study specific procedures.

Exclusion Criteria:

* Anticancer therapy (e.g. chemotherapy, radiotherapy (except for routine pre-operative radiotherapy for colorectal cancer), targeted therapy, concomitant systemic immune therapy, or any experimental therapy) within 4 weeks before inclusion;
* History of a clinically significant allergy;
* Circulating plasma concentration CEA ≥ 300 ng / ml;
* 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;
* Patients pregnant or breastfeeding (pregnancy should be ruled out by an assay of βhCG plasma within 4±1 weeks prior to administration of the conjugate), lack of effective contraception in male or female patients with reproductive potential;
* Laboratory abnormalities defined as:

Colorectal 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 Upper Limit Normal (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);
* 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;
* Any condition that the investigator considers to be potentially jeopardizing the patients' wellbeing or the study objectives.

Primary outcomes:
measure: Number of patients with treatment-related adverse events
timeFrame: up to 10 days after the surgery
Secondary outcomes:
measure: Tumor-to-background ratio (TBR) for fluorescence
timeFrame: day 4
measure: Serum SGM-101 concentrations
timeFrame: up to 1 month after surgery
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Cancer Institute
Study officials:
affiliation: Leiden University Medical Center
name: Alexander L Vahrmeijer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lwin TM, Hoffman RM, Bouvet M. The future of tumour-specific fluorescence-guided surgery for pancreatic cancer. Lancet Gastroenterol Hepatol. 2020 Aug;5(8):715-717. doi: 10.1016/S2468-1253(20)30123-0. Epub 2020 May 14. No abstract available.
citation: Schaap DP, de Valk KS, Deken MM, Meijer RPJ, Burggraaf J, Vahrmeijer AL, Kusters M; SGM-101 study group. Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer. Br J Surg. 2020 Mar;107(4):334-337. doi: 10.1002/bjs.11523. Epub 2020 Jan 21.
citation: Boogerd LSF, Hoogstins CES, Schaap DP, Kusters M, Handgraaf HJM, van der Valk MJM, Hilling DE, Holman FA, Peeters KCMJ, Mieog JSD, van de Velde CJH, Farina-Sarasqueta A, van Lijnschoten I, Framery B, Pelegrin A, Gutowski M, Nienhuijs SW, de Hingh IHJT, Nieuwenhuijzen GAP, Rutten HJT, Cailler F, Burggraaf J, Vahrmeijer AL. Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study. Lancet Gastroenterol Hepatol. 2018 Mar;3(3):181-191. doi: 10.1016/S2468-1253(17)30395-3. Epub 2018 Jan 30.