Study of AVB-620 in Women With Primary, Nonrecurrent Breast Cancer Undergoing Surgery

Study Overview
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Brief Summary
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Phase 2, open-label study of AVB-620 in women with primary, nonrecurrent and nonmetastatic breast cancer undergoing surgery.

Detailed Description
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Phase 2, open-label study of AVB-620 in women with primary, nonrecurrent, nonmetastatic breast cancer undergoing either a lumpectomy with simultaneous sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), or a mastectomy and simultaneous ALND. AVB-620 is a synthetic protease-activated peptide dye conjugate administered intravenously for the fluorescence detection and localization of potentially malignant tissue in primary tumor, tumor margins, or lymph nodes. A fluorescence image will be displayed on a monitor and will assist the surgeon to assess potentially cancerous tissue within the primary tumor site, tumor margins, or in lymph nodes which drain the primary tumor site. Eligible patients will receive a single dose of AVB-620 by IV infusion up to 24 hours prior to breast surgery. The study will evaluate the effect of timing of AVB-620 administration relative to surgery on the fluorescence and the accuracy of the AVB-620 imaging data to distinguish between malignant and nonmalignant tissues.

Official Title
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An Open-Label, Single-Arm, Phase 2 Study of AVB-620 in Women With Primary, Nonrecurrent Breast Cancer Undergoing Surgery

Conditions
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Primary Invasive Malignant Neoplasm of Female Breast, Carcinoma Breast, Breast Cancer Female, Carcinoma, Ductal, Breast, Stage II Breast Cancer, Stage I Breast Cancer, Stage III Breast Cancer

Intervention / Treatment
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* Device: Investigational Imaging device
* Drug: AVB-620


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DCIS or Stage I-III primary invasive carcinoma of the breast Primary surgical treatment is lumpectomy + SLNB or ALND --or-- mastectomy + ALND Signed written informed consent At least 18 years of age ECOG performance status 0 to 2 Life expectancy of at least 6 months Total bilirubin ≤ 2 mg/dL AST/SGOT and ALT/SGPT ≤ 2.5 X ULN Negative serum pregnancy test and using medically acceptable form of contraception if of child bearing potential LVEF within normal limits if patient received prior anthracycline therapy [Period 1]. Exclusion Criteria: Recurrent ipsilateral breast cancer Prior neoadjuvant chemotherapy, endocrine therapy, or biologic therapy for current breast cancer [Period 2] Prior neoadjuvant chemo or biologic therapy for current breast cancer within 4 weeks prior to planned surgery [Period 1] Open surgery in ipsilateral breast within 1 year. Prior malignancy, other than breast cancer, active within the last 6 months Prior radiation therapy to the chest [Period 2] Radiation therapy to ipsilateral breast [Period 1] Abnormal cardiac rhythm not controlled with medication; Hx of stroke within 1 year; Hx of coronary events and/or heart failure within 1 year. Diagnosis of autoimmune disorder, including RA, SLE, or Sjogren's syndrome Hx of drug-related anaphylactic reactions, severe allergic reactions related to drug; active diagnosis of uncontrolled airway hyperactivity, uncontrolled asthma, or asthma requiring oral corticosteroids. Hx of drug-induced acute tubular necrosis. Chronic renal failure or current evidence of moderate to severe renal impairment. Current diagnosis of any other active or clinically significant nonbreast cancer Received systemic investigational drug within 6 weeks prior to AVB-620 administration or has received AVB-620 previously. Pregnant or breast feeding or plans to become pregnant within 6 months of AVB-620 administration. Unresolved acute toxicity from prior anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Period 1 will enroll approximately 35 patients to evaluate conditions to achieve maximal differences in fluorescent signals between malignant and nonmalignant tissue. Period 2 will enroll approximately 120 patients to test dosing and imaging conditions determined in Period 1 and accuracy of AVB-620 imaging data to distinguish between malignant and nonmalignant tissues.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVB-620 & Investigational Imaging Device<br>Eligible subjects will receive a single dose of AVB-620 as intravenous infusion before the surgical procedure. During the surgical procedure, fluorescent imaging will be undertaken to distinguish between malignant and nonmalignant tissues. | Device: Investigational Imaging device<br>* Fluorescence imaging of the of the primary tumor specimen, any secondary breast specimens, and lymph nodes will be performed.<br>* Other names: Fluorescent Imaging Camera;Drug: AVB-620<br>* AVB-620 will be administered IV before the surgical procedure.<br>* Other names: Investigational Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the accuracy of AVB-620 imaging data to distinguish between malignant and nonmalignant tissues. | Determine the accuracy of AVB-620 in correlating image-identified malignant breast or lymph node tissue with pathology findings in breast cancer patients. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of AVB-620 as assessed by incidence of adverse events and abnormal laboratory values. | Evaluate the safety and tolerability of a single AVB-620 infusion in women undergoing breast cancer surgery. | 1 month | 
| Identify malignant tissue types that provide the most robust fluorescence response compared to non-malignant tissue. | Measure fluorescence intensity differences between malignant and non-malignant tissue to identify best responding tissue type. | 1 month | 
| Evaluate timing of AVB-620 administration on optical fluorescence characteristics | Further evaluate the effect of the timing of AVB-620 administration on the optical fluorescence characteristics | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast carcinoma, DCIS