VEGF-targeted Fluorescent Tracer Imaging in Breast Cancer

NCT ID: NCT01508572

Last Updated: 2017-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-01-31

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.

Conditions

Breast Cancer

Keywords

breast cancer; VEGF; optical imaging

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bevacizumab-IRDye800CW

In this two stage, non-randomized, non-blinded, prospective, multicenter feasibility study, bevacizumab-IRDye800CW will be administered to a total of 20 patients with proven breast cancer.

Group Type: EXPERIMENTAL

bevacizumab-IRDye800CW

Intervention Type: DRUG

In this two stage, non-randomized, non-blinded, prospective, multicenter feasibility study, bevacizumab-IRDye800CW will be administered to a total of 20 patients with proven breast cancer.

Interventions

bevacizumab-IRDye800CW

In this two stage, non-randomized, non-blinded, prospective, multicenter feasibility study, bevacizumab-IRDye800CW will be administered to a total of 20 patients with proven breast cancer.

Intervention Type: DRUG

Other Intervention Names

Fluorescence tracer imaging; Beva-800CW; Bevacizumab-800CW

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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UMC Utrecht

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

G.M. van Dam

Prof Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Go M. van Dam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

Other Identifiers

2011-003083-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UMCG/UMCU_01

Identifier Type: -

Identifier Source: org_study_id