Patients with breast cancer eligible for surgery
Conditions
Interventions
Product Name: Bevacizumab-800Cw
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: n/a
Other descriptive name: n/a
Conc
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or Female, aged = 18 years. 2. Confirmed diagnosis of breast cancer by means of histology or cytology and eligible for tumor resection surgery. 3. Tumor size = 5 mm (0, 5 cm) diameter according to anatomical imaging data. 4. WHO performance score 0-2. 5. Life expectancy greater than 12 weeks 6. Written informed consent has been obtained 7. In the Investigator’s opinion, patient is able and willing to comply with all trial requirements. For female subjects who are of childbearing potential, are premenopausal with intact reproductive organs or are less than 2 years post menopausal 8. A negative serum pregnancy test within 2 weeks prior to receiving the second generation tracer 9. Willing to ensure that she or her partner uses effective contraception during the trial and for 3 months thereafter. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Non palpable breast tumor 2. Breast prosthesis in the target breast 3. History of infusion reactions to Bevacizumab or other monocolonal antibody therapies 4. Concurrent anticancer therapy (chemotherapy, radiotherapy, vaccines, immunotherapy) delivered within the last 6 weeks prior to the start of the treatment 5. Unresolved chronic non-hematological toxicity higher than NCI-CTC grade 2 6. Participation in a clinical study involving an investigational drug or device within 30 days prior to the start of treatment 7. Significant renal or hepatic impairment. 8. Scheduled elective surgery, with the exception of the breast surgical procedure, or other procedures requiring general anaesthesia during the trial. 9. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 10. Inadequately controlled hypertension with or without current antihypertensive medications. 11. History of MI, TIA, CVA, pulmonary embolism, uncontrolled CHF, significant liver disease, unstable angina within 6 months prior to enrolment. 12. Patients receiving anticoagulant therapy with vitamin K antagonists. 13. Patients receiving Class IA or Class III antiarrhythmic agents. 14. Evidence of QT prolongation on pre treatment ECG (males >440ms, females>450 ms) 15. Magnesium, potassium and calcium levels below LLN which is regarded clinically relevant with regards to study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is an interventional exploratory open label dose escalation trial to be conducted in two trial centers. Studying the fluorescence signal in breast cancer tissue after administration of increasing doses of Bevacizumab-IRDye 800CW 1:2 conjugate (second generation tracer) in patients with confirmed breast cancer who are scheduled for tumor resection surgery or mastectomy. The aim of this study is to define the optimal dose of the tracer for the visualisation of intra operative tumor delineation. ;Timepoint(s) of evaluation of this end point: This end-point will be evaluated after surgery - post-hoc analyses of both the intraoperative required images of the wound bed and at the Dept of Pathology in-depth by fluorescence imaging;Secondary Objective: Asses the safety of the second generation conjugate at all doses tested. Compare conventional histo-pathological margin assessment with margin assessment using the fluorescent signal Confirm if fluorescent signal corresponds to tumor tissue Explore fluorescence intensity ex vivo in tumor and surrounding tissue Relate TBRs to plasma concentrations of complete tracer and fractions of unbound tracer components. ;Primary end point(s): • Tumor to Background Ratio (TBR) calculated from images taken intra-operatively • Tumor to Background Ratio (TBR) calculated from the bread loaf sliced excised specimen TBR is defined as the mean fluorescence intensity measured in the fluorescent region (tumor area) divided by the mean fluorescence intensity in the same image outside fluorescent region (non tumor area). Selection of endpoints To assess the success of intra operative tumor tissue delineation, the tumor to background ratios (TBR) will be calculated from images taken intra-operatively. A second ex vivo TBR will be calculated from bread loaf slices of the excised specimen. Microscopic histopathology and fluorescence microscopy will be done to confirm if the fluorescent signal corresponds to actual tumor tissu | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety variables will be any observed or reported adverse event from signing informed consent till the last study assessment. • Presence of positive margins as assessed by the surgeon intra operatively based on fluorescent images. • Presence of positive margins based on lump examination using the fluorescent signal • Tumor margins as obtained following standard histopathological practice • TBR calculated in microscopic slices in which tumor delineation is confirmed on adjacent H&E stained slides (Odyssey scanner, LICOR Inc, USA) • Fluorescence intensity in tumor and surrounding tissue is measured in fluorescent units (FU). Tumor-to-background ratios (TBR) are calculated post operatively in defined regions of interest (ROI) in the bread loaf specimens and histological slices. The variation in the signal at various increments distance of the tumor margin (0, 0.5, 1.0, 1.5, 2.0, and 2.5 up to 5 cm) will be expressed as percentage of the maximal fluorescence measured in the specimen. • Plasma concentration of the conjugate • Percentages of complete conjugate, free Bevacizumab and free IRDye 800 CW ;Timepoint(s) of evaluation of this end point: Time-points: screening visit (-7 +/-3 days) pre-surgery visit: injection of the tracer (-3 days) day-of-surgery: (day 0 ) post-surgery (12 +/-3 days) | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Surgery
University Medical Center Groningen
Outcome results
None listed