esophageal/gastric- or colorectal cancer
Conditions
Interventions
In part A (healthy volunteers), three dose levels comprising 1.5 mg, 6.0 mg
and 18.0 mg of VB5-845D-800CW will be investigated. The study drug will be
administered intravenously via an infusion
80 ml in 30 minutes.
In part B (patients), two dose levels comprising 6.0 mg and 18.0 mg of
VB5-845D-800CW will be evaluated during surgery. The study drug will be
administered intravenously via a
80 ml in 30 minutes.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Part A (healthy volunteers) A maximum of sixteen (16) healthy volunteers will take part in this study. Inclusion criteria 1) The subject is 18-65 years old at screening. 2) The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained before any study-related procedure is performed. 3) Female subjects need to be surgically sterile, post-menopausal or pre-menopausal with a negative urine pregnancy test at screening and just before administration of VB5-845D-800CW. Pre-menopausal female subjects have to agree to use an effective method of contraception for 90 days after administration. Male subjects have to agree to use an effective method of contraception for 90 days after administration. 4) The subject has a normal or clinically acceptable medical history, physical examination, and vital signs findings at screening. 5) The subject*s screening ECG and clinical laboratory test results are within normal limits, or if any are outside of normal limits they are considered to be clinically insignificant. 6) The subject has negative screening test results for hepatitis B, hepatitis C, and human immunodeficiency virus. 7) The subject has negative test results for drug and alcohol screening. 8) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Part B (patients) The study will be performed in maximum 18 patients. At each dose level 6 patients will be studied. An additional 6 patients will be included in the cohort with the most optimum dose level. Inclusion criteria 1) Patients > 18 years; 2) Patients capable and willing to give informed consent before study specific procedures; 3) Patients with suspected esophageal/gastric- or colorectal cancer, planned for an open or laparoscopic esophageal/gastric resection or colorectal resection respectively or transanal colorectal resection; 4) Normal and clinically acceptable medical history, medical physical examination and vital signs at screening; 5) The subject*s clinical laboratory tests are within normal limits, or if any are outside of normal limits they are considered to be clinically insignificant; 6) Absence of any physiological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Exclusion criteria
Exclusion criteria: Part A (healthy volunteers) A maximum of sixteen (16) healthy volunteers will take part in this study. , Exclusion criteria 1) Female subjects that are lactating or pregnant. 2) Unacceptable known diagnoses or diseases at baseline, e.g., known cardiovascular or pulmonary disease, renal or liver dysfunction, ECG or laboratory abnormalities, etc. 3) Use of prescription drugs, with the exception of contraceptive drugs. 4) Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year. 5) History of significant allergies or anaphylactic reactions. Part B (patients) The study will be performed in maximum 18 patients. At each dose level 6 patients will be studied. An additional 6 patients will be included in the cohort with the most optimum dose level. Exclusion criteria Patients will be excluded if any of the criteria below apply: 1) History of a clinically significant allergy or anaphylactic reactions; 2) Patients pregnant or breastfeeding; 3) Any condition that the investigator considers to be potentially jeopardizing the patients well-being or the study objectives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability endpoints - Treatment-emergent (serious) adverse events ((S)AEs). - Concomitant medication - Clinical laboratory tests o Haematology o Chemistry o Coagulation o Urinalysis - Vital signs o Pulse Rate (bpm) o Systolic blood pressure (mmHg) o Diastolic blood pressure (mmHg) o Body temperature o Peripheral oxygen saturation o Respiratory rate - Clinical examination, including assessment of injection site - ECG o Heart Rate (HR) (bpm), PR, QRS, QT, QTC | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy endpoints Dosing endpoints - The optimal dose of VB5-845D-800CW will be based on the mean difference in fluorescent signal (mean fluorescence intensity) between the tumor and surrounding tissue, also known as the tumor-to-background ratio (TBR). Other endpoints - Expression of EpCAM in the lesions. - Concordance rate between the pathology results with respect to the presence of cancer, EpCAM expression and the imaging signal. - Immunohistochemistry will be scored on intensity using a 3-point score: 0 is no expression, 1 minimal expression, 2 moderate expression and 3 strong expression. Pharmacokinetics endpoints The following endpoints will be determined for VB5-845D-800CW following each treatment. They will be derived by non-compartimental analysis (NCA) of the serum concentration-time data: - The area under the serum concentration-time curve from zero to infinity(AUC0-inf); - The maximum serum concentration (Cmax); - The area under the serum concentration-time curve from zero to t of the last measured concentration above the limit of quantification (AUC0-last); - The time to reach maximum plasma concentration (tmax); - The terminal disposition rate constant (*z) with the respective half-life (t*). - Other parameters, including Vz/F, CL/F, and other parameters as appropriate, as well as dose adjusted parameters, may be determined. For the urine samples, the cumulative urine excretion of VB5-845D-800CW, expressed as the percentage of the injected dose will be determined. | — |
Countries
Netherlands
Outcome results
None listed