Drug Safety ; Drug Specificity Clinical Trial
Official title:
Cetuximab - IRDye800 Intraoperative Fluorescence Imaging in Esophagectomy of Esophageal Cancer:A Single Center Clinical Research
The esophageal squamous cell carcinoma (ESCC) has high prevalence and mortality in China,
which become a severe challenge for public health. The molecular imaging technology has been
developed for intra-operative visualization and precise resection of the tumors. The imaging
probe possess high affinity to the tumor specific targets. Among the tumor related proteins,
EGFR is located on the cell membrane and over expresses in more than 50% ESCC which has been
used as an ideal target for molecular imaging.
Cetuximab is an EGFR targeting antibody for anti cancer therapy. When labeled with an
commercial available fluorescence dye IRDye800, cetuximab has been used as molecular imaging
probe in clinical trials for surgical navigation of cancers including head and neck squamous
cell cancers and gliomas. Previous studies shown high safety when using this probe and
excellence sensitivity for cancer detection, which bring great promise in translational
medicine.
This is a single-center prospective sequential trial. It is the first attempt to apply
cetuximab-IRDye800 probe in ESCC surgery. This probe will be produced under clinical Good
Manufacturing Practice (cGMP) conditions. The ESCC patients will be recruited with strict
criteria.Patients population is planned to be 40 cases between18 and 65 years old, without
gender limit. The patients will be divided into four groups : control group without probe
administration, 1% dose group (1% of therapeutic cetuximab dose; 2.5 Mg/m2) and 10% dose
groups (10%of therapeutic cetuximab dose ;25mg/m2) and 25% dose group (25%of therapeutic
cetuximab dose; 62.5mg/m2), 10 cases are sequential assigned to each group. After informed
consent, patients will receive a systemic infusion of the study drug 2 days before surgery.
Primary (safety and efficiency) and secondary endpoints (tissue EGFR expression) will be
recorded. Preoperative management and surgical procedures will been performed according to
conventional protocols. Intra-operative imaging of the surgical field will be performed in
real time at 2 time points: before and post tumor resection. The postoperative specimens will
be subjected to pathological analysis including correlation study of fluorescence signal and
tumor tissue in pathology slice.
A protocol for managing any allergic reaction related to systemic infusion of cetuximab has
been established. The patient's vital signs and ECG will be closely monitored post probe
administration. The blood, liver and kidney, coagulation function and cardiotoxicity will be
evaluated before and post surgery.
This clinical trial is anticipated to validate the concept that intra-operative fluorescent
imaging of esophageal squamous cell carcinoma with cetuximab-IRDye800 can facilitate the
demarcation of tumor boundary and identification of metastatic lymph nodes and testify its
safety.
| Status | Recruiting |
| Enrollment | 40 |
| Est. completion date | November 30, 2021 |
| Est. primary completion date | November 30, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility |
Inclusion Criteria: 1.18 years old = age = 65 years old, gender is not limited; 2. Esophageal squamous cell carcinoma confirmed by cytology or histology and requiring surgical treatment; 3. Preoperative high-grade gastroscopy confirmed that the tumor staging was T1-3N0-1M0 patients feasible for surgical resection; 4. The main organ function is basically normal: Karnofsky score >70%; 5. Laboratory blood tests meet surgical safety standards; 6. Informed consent form is signed before the study, the patient and / or their legal representative have the ability to fully understand the content of the trial, the process and possible adverse reactions, and the patients are able to comply for regular visit; 7. Women of reproductive age must have a negative pregnancy test and are not breastfeeding, both men and women need to receive contraceptive methods approved by the investigator and agree to maintain this contraceptive from the date of signing the informed consent to the end of the study. Exclusion Criteria: 1. Cetuximab drug allergy sufferers; 2. Preoperative electrocardiogram indicates patients with prolonged QTc interval; 3. People with mental or neurological diseases; 4. Patients with cachexia and severe malnutrition; 5. Patients with surgical contraindications such as coagulopathy, HIV antibody positive, and severely poorly controlled clinical infections; 6. Patients with other combined diseases (such as abnormal liver and kidney function) or combined medications, which may be affected by the investigator. 7. Patients who are simultaneously involved in another clinical study; |
| Country | Name | City | State |
|---|---|---|---|
| China | The Fifth Affiliated Hospital of Sun Yat-sen University | Zhuhai | Guangdong |
| Lead Sponsor | Collaborator |
|---|---|
| Fifth Affiliated Hospital, Sun Yat-Sen University |
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Tumor to Background Ratio | Tumor to Background Ratio by mean fluorescence intensity in tumor tissue and lymph nodes | intra-operative | |
| Primary | relative adverse drug reaction | relative adverse drug reaction after using cetuximab-IRDye800 | 14 days after using cetuximab-IRDye800 |