Clinical trial NCT01508572: VEGF-targeted Fluorescent Tracer Imaging in Breast Cancer
Official title: Validation of Uptake of a VEGF-targeted Optical Fluorescent Imaging Tracer in Surgical Specimens of Breast Cancer and Application of Pre- and Intra-operative Human Molecular Fluorescence Imaging Techniques. A Multicenter Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: breast cancer
VEGF
optical imaging
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
First posted: 2012-01-12
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the uptake, (semi-)quantification and localization of the VEGF targeting fluorescent tracer bevacizumab-IDRye800CW in breast cancer tissue, surrounding healthy tissue, tumor margins and lymph nodes. This is measured in surgical specimens after a single intravenous administration of 4,5 bevacizumab-IDRye800CW, using fluorescence microscopy and macroscopy techniques. Also the safety of bevacizumab-IDRye800CW is assessed. Another purpose is to assess the abilities of three different fluorescent signal detection systems to detect the fluorescent signal pre- and intra-operatively.

Detailed description: There is a need for better visualization of presence and extent of breast cancer to improve breast cancer management. Molecular imaging of breast cancer associated targets is a promising method to improve visualization. Vascular endothelial growth factor (VEGF) has proven to be a valid target for molecular imaging with radioactive labeled tracers. However in view of radiation safety, infrastructure, costs and stability, fluorescent labeling of bevacizumab (a VEGF targeting humanized monoclonal antibody) has potential advantages over radioactive labeling. Therefore recently the near-infrared fluorescent tracer bevacizumab-IRDye 800CW has been developed. In mice the fluorescent signal was clearly present in tumor tissue and could be visualized intra-operatively. The tracer was also approved for administration to patients in a microdose (tracer dose).

In this prospective multicenter feasibility study the new tracer bevacizumab-IRDye 800CW will be administered to a maximum of 30 patients with proven breast cancer 3 days before surgery. Part of the surgical specimen will after surgery extensively be investigated by macroscopy and microscopy to determine the uptake of the tracer in tumor tissue, surrounding normal tissue and lymph nodes. To detect the tracer before surgery, two different pre-operative imaging methods are used: MSOT (in the UMCG en FDOT in the UMCU. During surgery the intra-operative MFRI camera is available at both centers to detect the fluorescent signal.

The study consists of a total of five study procedure related patient visits.

1. During a screening visit, eligibility will be evaluated and patient characteristics will be collected.
2. During the administration visit, 3 days before surgery, 4.5 mg of bevacizumab-IRDye 800CW will be administered intravenously, followed by 4 hours observation. Also before and 4 hours after tracer injection pre-operative optical imaging will take place (in the UMC Groningen, the hand-held MSOT system will be used and in the UMC Utrecht, the FDOT system will be used) and blood samples are taken.
3. A third visit, approximately 36 hours after tracer administration, another pre-operative optical imaging procedure will take place.
4. At the day of surgery, first a blood sample will be taken and the last pre-operative optical imaging procedure will take place, followed by standard surgery. During surgery, the MFRI camera will be used to detect a fluorescent signal before and after incision an after removal of the tumor. Part of the surgical specimen will after surgery extensively be investigated by macroscopy and microscopy to determine the uptake of the tracer in tumor tissue, surrounding normal tissue and lymph nodes.
5. At an outpatient visit (approximately 10 days after surgery) (visit 5), the last blood sample will be taken.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Patients with proven breast cancer (cytology, histology) who are scheduled to receive operation intervention.
* Tumor size of at least 15 mm diameter according to anatomical imaging data.
* Signed written informed consent.
* Able to comply with the protocol.
* WHO performance score 0-2.

Exclusion Criteria:

* Other invasive malignancy.
* Serious other medical conditions.
* Pregnant or lactating women. (Documentation of a negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause).
* Prior radiotherapy on the involved area.
* Major surgery within 28 days before the initiation of the study.
* Prior allergic reaction to immunoglobulins or immunoglobulin allergy.
* Prior neo-adjuvant chemotherapy.
* Breast prosthesis in target breast.

UMC Utrecht (FDOT) specific exclusion criteria

* Breast is too big to fit in the biggest cup or is too small to fit in the smallest cup of the FDOT system.
* Non-intact skin at time of the FDOT procedures.
* Breast located skin diseases.
* Piercings or tattoos located on the breast/nipple.
* Contra-indication for MR procedures or claustrophobia.
* Inability to lay prone positioned for the duration of the FDOT procedure (10 minutes) and MR procedure (30 minutes).
* Tumor located close to the chest wall as assessed by breast imaging data.

Primary outcomes:
measure: The uptake of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes in surgical specimens by fluorescence microscopy and macroscopy
timeFrame: After the last patient is included, which is expected to be within one year after the first inclusion
measure: Occurrence of adverse events as a measure of safety and tolerability of bevacizumab-IRDye800CW
timeFrame: Participants will be observed for the duration of hospital stay, an expected average of 4 hours after tracer injection. In case of adverse events, patients are observed and treated until recovery
Secondary outcomes:
measure: Detection ability of preoperative optical fluorescence imaging techniques (FDOT; Fluorescence diffuse optical tomography and MSOT; multispectral opto-acoustic imaging) of the fluorescent signal from bevacizumab-IRDye800CW
timeFrame: detection of the tracer is performed at 4h, 36h and 72h after tracer injection.
measure: Detection ability of the intra-operative mulitspectral fluorescence reflectance imaging (MFRI) of the fluorescent signal from bevacizumab-IRDye 800CW during surgery
timeFrame: 72 hours after tracter injection, during surgery.
measure: Detection ability of all optical imaging techniques (FDOT, MSOT, MFRI) of the fluorescent signal in surgical specimens ex vivo
timeFrame: after the last patient is operated, which is approximately one year after study start.
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Go M. van Dam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: