Improvement of the Operative Outcome in Patients With Primary VEGF + Unifocal Breast Cancer or DCIS Through the Intraoperative Visualization of the Tumor Using Molecular Imaging and Bevacizumab-IRDye-800CW (DoT-FMI)

Improvement of the Operative Outcome in Patients With Primary VEGF Positive Unifocal Breast Cancer or Ductal Carcinoma in Situ (DCIS) Through the Intraoperative Visualization of the Tumor Using Molecular Imaging and Fluorescent Markers Bevacizumab-IRDye-800CW

It is a prospective, open, non-randomized, multicenter, one-armed, blinded (surgeon), diagnostic clinical trial according to AMG and MPG. The fluorescent marker Bevacizumab-IRDye800CW has advantages over conventional methods of tumor imaging in terms of accuracy, patient safety and validity. In order to be able to detect this marker in vivo, special multispectral fluorescence-reflecting cameras (MFRI) were developed, which can be used for the intraoperative display of the tumor and potentially affected lymph nodes and which are now to be evaluated together with the fluorescence marker.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Bevacizumab-IRDye800CW

Detailed Description

Complete surgical excision of the tumor (R0 resection) is the cornerstone of any curative therapy concept for cancer. In order to be able to achieve the highest possible rate of R0 resections, the tumor, its localization and spread needs to be more precisely represented. This should be possible through an intraoperative representation of the tumor by means of fluorescence imaging at the molecular level.

Vascular Endothelial Growth Factor (VEGF, or VEGF-A), which is expressed differently in normal and tumor tissue, is a suitable marker for molecular imaging, especially in gynecological cancer. Bevacizumab is a genetically engineered humanized monoclonal antibody that is directed against VEGF and is already therapeutically approved for the treatment of breast and ovarian cancer and has also shown efficacy in studies on endometrial cancer.

Fluorescence-labeled bevacizumab has advantages over conventional methods of tumor imaging in terms of accuracy, patient safety, cost efficiency and validity. A fluorescent marker, Bevacizumab-IRDye800CW, was developed and recently used in clinical trials in the Netherlands. In order to be able to detect this marker in vivo, special multispectral fluorescence-reflecting cameras (MFRI) were developed, which can be used for intraoperative visualization of the tumor and potentially affected lymph nodes. These systems can now be used to evaluate the fluorescent marker in clinical studies.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• women of age ≥ 18 years able to give consent who have been informed in detail about the study beforehand and have given written consent to participate
• Patients with histologically confirmed unifocal VEGF-positive invasive breast cancer with an indication for BET
• Patients with histologically confirmed unilateral VEGF-positive DCIS with an indication for BET
• ECOG performance ≤ 2
• Pre-menopausal women had a negative pregnancy test prior to administration of the study medication
• Negative pregnancy test (serum) within 10 days prior to administration of the test medication in all women of childbearing age with results available prior to the start of therapy (or postmenopausal; age ≥60 and no menses over ≥ 1 year without any other medical cause; or hysterectomy, or tube ligation, or bilaterally guided occlusion). Women of childbearing potential who are sexually active must agree that they and their partner may use effective contraception during the trial and for 3 months after participation

Exclusion Criteria:

• Second malignancy in the breast and other organs
• Pregnant or breastfeeding patients
• Planned sentinel lymph node marking using patent blue
• Previous radiation therapy in the area to be examined
• Known or suspected hypersensitivity to the study medication (according to IMPD / SmPC) or other immunoglobulins
• Currently after neoadjuvant (primarily systemic) chemotherapy and anti-hormone therapy
• Immunotherapy (e.g. monoclonal antibodies, cytokines or signal transduction inhibitors) in the last 28 days prior to the declaration of consent
• Previous therapy with bevacizumab
• Planned reconstruction in the breast to be examined
• Previous surgery within the last 28 days prior to the declaration of consent
• Non-healing wounds, ulcers or broken bones within the last 28 days prior to giving informed consent
• Patients with ileus within the last 28 days prior to the declaration of consent
• Non-adjustable hypertension (> 145/90 mmHg) despite optimal drug therapy
• Insufficient kidney function (serum creatinine> 1.5 x upper limit of the normal range)
• Current or recent treatment with another investigational drug in another clinical trial within 28 days of informed consent
• Potentially fertile women without adequate contraception. Safe contraceptive measures are procedures with a Pearl index of ≤ 1%
• Patients with other serious illnesses that pose an unreasonable risk for participating in the study
• Persons who are in a dependent / employment relationship with the sponsor or investigator
• Persons who are to be or are to be accommodated in an institution due to a court or official order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment arm

Drug: Bevacizumab-IRDye800CW; In order to be able to detect this marker in vivo, special multispectral fluorescence-reflecting cameras (MFRI) were developed, which can be used for the intraoperative display of the tumor and potentially affected lymph nodes and which are now to be evaluated together with the fluorescence marker.; Other Names: Device: special multispectral fluorescence-reflecting cameras

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the sensitivity and specificity of bevacizumab- IRDye800CW	Determination of the sensitivity and specificity of bevacizumab- IRDye800CW with regard to the identification of the tumor margins compared with the histopathological findings (resection result R0, R1) as the gold standard	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Toxicity of Bevacizumab-IRDye800CW will be analyzed by absolute and relative frequencies of Safety events	Absolute and relative frequencies of AE, SAE, AR, and SAR are presented by MedDRA System Organ Class and Preferred Term.	21 days

Collaborators and Investigators

• Sponsor: Technical University of Munich

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: DOT-1871-KIE-0120-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: no patient specific data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No