Real-time Intraoperative Breast Cancer Visualization for Margin Assessment
Study Details
Study Description
Brief Summary
The investigators' preclinical data have demonstrated the feasibility of fluorescence-guided tumor resection by Cancer Vision Goggles (CVG) with LS301 in animal models. In this study, the investigators will conduct intraoperative imaging procedures that have minimal interference with ongoing surgery. The underlying hypothesis is that the accurate detection of all cancer cells highlighted by LS301 during surgery will reduce the number of breast cancer patients with margin positivity to less than 5%, compared to the current surgical paradigm of greater than 20%. The pilot study will obtain critical data required to address the larger question of surgical margin assessment in a full Phase I clinical trial.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I Dose Level 1: LS301 Patient will undergo surgery 4-24 hours after administration of LS301 (0.05 mg/kg) Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. |
Drug: LS301
-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.
Device: Cancer Vision Goggles
-Member of operating team will wear during surgery
Other Names:
Procedure: Surgery
-Standard of care
|
| Experimental: Phase I Dose Level 2: LS301 Patient will undergo surgery 4-24 hours after administration of LS301 (0.075 mg/kg) Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. |
Drug: LS301
-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.
Device: Cancer Vision Goggles
-Member of operating team will wear during surgery
Other Names:
Procedure: Surgery
-Standard of care
|
| Experimental: Phase I Dose Level 3: LS301 Patient will undergo surgery 4-24 hours after administration of LS301 (0.1 mg/kg) Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. |
Drug: LS301
-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.
Device: Cancer Vision Goggles
-Member of operating team will wear during surgery
Other Names:
Procedure: Surgery
-Standard of care
|
| Experimental: Phase I Dose Expansion: LS301 Patient will undergo surgery 4-24 hours after administration of LS301 (dose to be determined in Phase I dose escalation portion) 9 patients will be enrolled (6 invasive ductal carcinoma and 3 DCIS) Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. |
Drug: LS301
-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.
Device: Cancer Vision Goggles
-Member of operating team will wear during surgery
Other Names:
Procedure: Surgery
-Standard of care
|
| Experimental: Phase II: LS301 Patient will undergo surgery 4-24 hours after administration of LS301 (dose to be determined in Phase I portion) Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. |
Drug: LS301
-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.
Device: Cancer Vision Goggles
-Member of operating team will wear during surgery
Other Names:
Procedure: Surgery
-Standard of care
|
Outcome Measures
Primary Outcome Measures
- Safety of LS301 in breast as measured by related adverse events (Phase I) [Time of injection to 3 hours post-injection]
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
- Optimal imaging dose of LS301 (Phase I) [Completion of enrollment of all Phase I participants (estimated to be 18 months)]
Optimal dose will be the dose at which fewer than 2 dose-limiting toxicities (DLTs) are observed and optimal image quality is observed. It need not be the maximum tolerated dose (MTD) if optimal image quality is observed at a lower dose than the MTD. DLT is defined as any grade 2 or above toxicity that occurs during the hour after injection that is considered possibly, probably, or definitely related to LS301 Toxicities will be graded using the NCI Common Terminology Criteria for Adverse Events version 5.0
- Ability of LS301 to predict presence of positive margins around partial mastectomy (Phase II) [Day 1 (at the time of surgery)]
-The histopathological results of margin positivity has the following possible results: margin negative, margin positive at LS301 and CVG identified locations, margin positive at LS301 and CVG unidentified locations. Using LS301 and CVG, the exercised tissue will be considered to be margin positive and have ink marked at the identified locations if any positive margins are observed; otherwise, the margin is considered negative. Diagnostic test characteristics (sensitivity and specificity) of LS301 and CVG for margin positivity by histology will established and margin positivity rate, defined as the proportion of tumors with histopathologically confirmed positive margins but missed by CVG, will be estimated.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Newly diagnosed Stage I-II breast cancer patients undergoing breast-conserving therapy and SLN biopsy.
-
Negative nodal basin clinical exam.
-
At least 18 years of age.
-
Able to understand and willing to sign a written informed consent document.
Exclusion Criteria:
-
Contraindications for surgery.
-
Receiving any investigational agents.
-
History of allergic reactions attributed to ICG or other agents used in the study, include known iodide or seafood allergy. The investigators do not expect many of these adverse reactions with LS301 because it is not radioactive and does not possess iodinated counter ions.
-
Presence of underlying lung disease
-
Pregnant. Female patients of childbearing potential must have a negative serum or urine pregnancy test no more than 7 days before start of participation.
-
Breastfeeding. Patients who are breastfeeding are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LS301.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
- Kingdom Capital
Investigators
- Principal Investigator: Julie Margenthaler, M.D., Washington University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 201907135