Breast CancerPhase 1NCT01508572
VEGF-targeted Fluorescent Tracer Imaging in Breast Cancer
A Phase 1 study testing bevacizumab-IRDye800CW in people with Breast Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- bevacizumab-IRDye800CW
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2011to Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- During a screening visit, eligibility will be evaluated and patient characteristics will be collected.
- 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.
- A third visit, approximately 36 hours after tracer administration, another pre-operative optical imaging procedure will take place.
- 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.
- At an outpatient visit (approximately 10 days after surgery) (visit 5), the last blood sample will be taken.
- Conditions
- Breast Cancer
- Being tested
- bevacizumab-IRDye800CW
- Keywords
- breast cancer, VEGF, optical imaging
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumab-IRDye800CWDrug
Also called Fluorescence tracer imaging, Beva-800CW, Bevacizumab-800CW
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.
| Study group | Role | What they receive |
|---|---|---|
| bevacizumab-IRDye800CW | Experimental | 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. Receives: Drug: bevacizumab-IRDye800CW |
What is being measured
The primary outcome is the main question the study is designed to answer.
The uptake of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes in surgical specimens by fluorescence microscopy and macroscopy
Outcome measures:
- The accumulation, tissue distribution, lokalization and (semi) quantification of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes. Measured by macroscopy using MSOT, Odessey and MFRI and by microscopy using fluorescence microscope and Odessey.
- Correlation of the above to VEGF-levels and other biological parameters.
Measured: After the last patient is included, which is expected to be within one year after the first inclusion
Occurrence of adverse events as a measure of safety and tolerability of bevacizumab-IRDye800CW
Obtaining information on safety aspects of bevacizumab-IRDye 800CW, side effects, AE, SAE, SUSAR by observing patients after tracer injection and follow up until 14 days after surgery
Measured: 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 (3)
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
- To assess and compare the presence of a fluorescent signal in breast cancer tissue and normal tissue
- To explore pharmacokinetics and optical imaging time-points by peforming FDOT/MSOT at multiple time points after administration.
- To correlate the fluorescence signal assessed by FDOT/MSOT with VEGF-levels, other biological parameters and the fluorescent signal assessed in the ex-vivo surgical specimen.
Measured: detection of the tracer is performed at 4h, 36h and 72h after tracer injection.
Detection ability of the intra-operative mulitspectral fluorescence reflectance imaging (MFRI) of the fluorescent signal from bevacizumab-IRDye 800CW during surgery
- To assess and compare the presence of a fluorescent signal in breast cancer tissue and normal tissue by assessing the images made by the MFRI during and after surgery.
- the fluorescent signal assessed by MFRI will be correlated with VEGF levels in the ex-vivo surgical specimens.
Measured: 72 hours after tracter injection, during surgery.
Detection ability of all optical imaging techniques (FDOT, MSOT, MFRI) of the fluorescent signal in surgical specimens ex vivo
Assessment of the ability of all optical imaging techniques (FDOT, MSOT, MFRI) to detect fluorescent signal in surgical specimens ex vivo by (semi) quantification of the images and to compare images between different techniques and different tissues (surrounding tissue, tumor tissue and lymph nodes)
Measured: after the last patient is operated, which is approximately one year after study start.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2012 (estimated)
- Study startOct 2011
- Primary completionNov 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht
- Responsible party
- Principal investigator, G.M. van Dam, University Medical Center Groningen
- Investigators
- Go M. van Dam, MD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01508572
- Sponsor's protocol ID
- UMCG/UMCU_01
- Other IDs
- 2011-003083-75
- Status last verified
- Oct 2017
- First submitted
- 22 Dec 2011
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01508572
- Acronym / sponsor ID
- UMCG/UMCU_01
- Conditions
- Breast Cancer
- Keywords
- breast cancer, VEGF, optical imaging
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- UMC Utrecht
- Study start
- Oct 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 12 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- During a screening visit, eligibility will be evaluated and patient characteristics will be collected.
- 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.
- A third visit, approximately 36 hours after tracer administration, another pre-operative optical imaging procedure will take place.
- 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.
- At an outpatient visit (approximately 10 days after surgery) (visit 5), the last blood sample will be taken.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bevacizumab-IRDye800CW | Experimental | Drug: bevacizumab-IRDye800CWIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab-IRDye800CWAlso: Fluorescence tracer imaging, Beva-800CW, Bevacizumab-800CWIn 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. | Drug | bevacizumab-IRDye800CW |
Primary outcome
The uptake of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes in surgical specimens by fluorescence microscopy and macroscopy
Time frame: After the last patient is included, which is expected to be within one year after the first inclusion
Outcome measures: * The accumulation, tissue distribution, lokalization and (semi) quantification of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes. Measured by macroscopy using MSOT, Odessey and MFRI and by microscopy using fluorescence microscope and Odessey. * Correlation of the above to VEGF-levels and other biological parameters.
Occurrence of adverse events as a measure of safety and tolerability of bevacizumab-IRDye800CW
Time frame: 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
Obtaining information on safety aspects of bevacizumab-IRDye 800CW, side effects, AE, SAE, SUSAR by observing patients after tracer injection and follow up until 14 days after surgery
3 secondary outcomes
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
Time frame: detection of the tracer is performed at 4h, 36h and 72h after tracer injection.
Detection ability of the intra-operative mulitspectral fluorescence reflectance imaging (MFRI) of the fluorescent signal from bevacizumab-IRDye 800CW during surgery
Time frame: 72 hours after tracter injection, during surgery.
Detection ability of all optical imaging techniques (FDOT, MSOT, MFRI) of the fluorescent signal in surgical specimens ex vivo
Time frame: after the last patient is operated, which is approximately one year after study start.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Go M. van Dam, MD, PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bevacizumab-IRDye800CW in people with Breast Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The uptake of bevacizumab-IRDye800CW in breast cancer tissue, surrounding tissue and lymph nodes in surgical specimens by fluorescence microscopy and macroscopy (time frame: After the last patient is included, which is expected to be within one year after the first inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.