FLuoresence Image Guided Surgery With A VEGF-targeted Tracer in Soft-tissue Sarcomas in Humans Approach With Bevacizumab-IRDye 800CW

Study Overview
=================
Brief Summary
-----------------
There is a need for better visualization of resection margins during surgery for soft tissue sarcoma. Optical molecular imaging of soft tissue sarcoma associated biomarkers is a promising technique to accommodate this need. The biomarker Vascular Endothelial Growth Factor (VEGF-A) is overexpressed in soft tissue sarcoma versus normal tissue and has proven to be a valid target for molecular imaging. VEGF-A can be targeted by the monoclonal antibody bevacizumab. Monoclonal antibodies can be labeled by the near-infrared (NIR) fluorescent dye IRDye800CW (800CW). The investigators hypothesize that bevacizumab-800CW accumulates in VEGF expressing cancer, enabling soft tissue sarcoma visualization using a NIR intraoperative camera system. In this pilot intervention study the investigators will determine the optimal dosage of bevacizumab-800CW (10, 25 or 50mg) to detect soft tissue sarcoma intraoperatively.

Official Title
-----------------
FLuoresence Image Guided Surgery With A VEGF-targeted Tracer in Soft-tissue Sarcomas in Humans (FLASH)- A Feasibility Dose Escalation Study

Conditions
-----------------
Soft Tissue Sarcoma

Intervention / Treatment
-----------------
* Drug: Bevacizumab-IRDye800CW


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years. Patients with soft tissue sarcoma who are scheduled to undergo surgical intervention with curative intent World Health Organization (WHO) performance score 0-2. Signed written informed consent Exclusion Criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent. Other invasive malignancy Pregnant or lactating women. Documentation of a negative pregnancy test must be available for woman of childbearing potential. Woman of childbearing potential are pre- menopausal women with intact reproductive organs and women less than two years after menopause. History of infusion reactions to bevacizumab or other monoclonal antibody therapies. Inadequately controlled hypertension with or without current antihypertensive medications Within 6 months prior to inclusion: myocardial infarction, Transient Ischemic Attack, Cerebral Vascular Accident, pulmonary embolism, uncontrolled chronic hepatic failure, unstable angina pectoris.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: phase I/II safety and dose-finding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Bevacizumab-IRDye800CW | Drug: Bevacizumab-IRDye800CW<br>* dose finding:10mg; 25mg; 50mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tracer detection | Determine if accumulation of the fluorescent tracer bevacizumab-800CW can be detected with an intraoperative near infrared camera system to identify soft tissue sarcoma tissue during surgery | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Dose finding | Identify two doses of the NIR antibody tracer conjugate that provide the best visualization of tumour tissue during surgery | up to 6 months | 
| Part 1: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | To obtain information safety aspects of the tracer, side effects, adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR) | up to 6 months | 
| Part 2: Optimal dose | Define which of the two doses of conjugate identified in part 1 is the optimal dose for further development in a phase II trial | up to 6 months |