Real-time Intraoperative Breast Cancer Visualization for Margin Assessment

NCT ID: NCT02807597

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-18
• Study Completion Date: 2022-01-27

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.

Phase 1: to determine the safety and optimal imaging dose of LS301 injected in breast cancer patients.

Phase 2: to determine the ability of this novel fluorescence imaging agent to predict the presence of positive margins around partial mastectomy specimens and positive SLNs during surgical therapy for breast cancer.

Detailed Description

A rolling six design which is intended for relatively safe trials and shortening the study duration is proposed for the phase 1 portion 74. In the rolling six design, three to six patients can be enrolled to a dose each time. The dose de-escalation occurs when two or more DLT occur at a dose level while dose escalation occurs when 3/3, 4/4, 5/5, 5/6 or 6/6 patients are evaluated without DLT 75. Three dose levels will be tested in the phase I study, 0.05, 0.075 and 0.10 mg/kg. LS301 will be administered intravenously at a starting dose of 0.05 mg/kg to a cohort of six patients and escalate/de-escalate following the decision rule of the rolling six design. Once six patients have been included at the current dose level, inclusions are suspended until at least five of the six patients have completed the procedure without DLT observed in the evaluation period. MTD is hit where two or more patients out of six at a dose level experience DLT. The investigators do not expect any serious adverse events related to LS301 at the initial Dose Level 1. Once the MTD is determined, an expansion cohort with 9 patients will be tested at the MTD and an optimal imaging dose will be recommended for the subsequent phase II trial.

At the completion of the expansion cohort, a single arm phase 2 trial will be performed at the optimal imaging dose. A breast surgeon will perform breast conserving surgery per standard of care. At the completion of the surgery, a second investigator (to reduce bias in data collection) will wear the cancer vision goggle (CVG) to visualize the excised tissue to determine if there are any positive margins based on the presence of LS301 fluorescence. If any positive margins are observed, the subject will be considered to have a positive margin; otherwise, the margin is considered negative. The excised tissue will later be examined by a breast cancer pathologist. Standard pathologic techniques will be used to determine if there are positive margins. Particular attention will be paid to the sites marked following CVG assessment to confirm whether the margin is positive or negative at any of these sites, or positive at other locations not identified by CVG. No interventions will be allowed based on the CVG results.

This study was initiated at Washington University in St. Louis and is being transferred to UTSW. Phase 1a was initiated at Washington University in St. Louis where 9 subjects were enrolled. The PI is continuing with Phase 1B at UTSW where 9 more subjects will be enrolled. Once completed, the results of Phase 1 (a and b) will be sent to the FDA for review. Phase II will begin once the FDA has reviewed the interim data and authorized Phase II to open. After phase 1 data has been submitted to and discussed with the FDA, an additional cohort of 88 patients will be enrolled to the phase 2 portion of the trial to assess the diagnostic capabilities of LS301 for identification of positive margins at surgery. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Conditions

Breast Cancer; Cancer of the Breast

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group Type: EXPERIMENTAL

LS301

Intervention Type: DRUG

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Cancer Vision Goggles and standard fluorescence imaging systems

Intervention Type: DEVICE

-Member of the operating team will wear the CVG during surgery

Surgery

Intervention Type: PROCEDURE

-Standard of care

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. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group Type: EXPERIMENTAL

LS301

Intervention Type: DRUG

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Cancer Vision Goggles and standard fluorescence imaging systems

Intervention Type: DEVICE

-Member of the operating team will wear the CVG during surgery

Surgery

Intervention Type: PROCEDURE

-Standard of care

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. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group Type: EXPERIMENTAL

LS301

Intervention Type: DRUG

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Cancer Vision Goggles and standard fluorescence imaging systems

Intervention Type: DEVICE

-Member of the operating team will wear the CVG during surgery

Surgery

Intervention Type: PROCEDURE

-Standard of care

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. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group Type: EXPERIMENTAL

LS301

Intervention Type: DRUG

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Cancer Vision Goggles and standard fluorescence imaging systems

Intervention Type: DEVICE

-Member of the operating team will wear the CVG during surgery

Surgery

Intervention Type: PROCEDURE

-Standard of care

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. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group Type: EXPERIMENTAL

LS301

Intervention Type: DRUG

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Cancer Vision Goggles and standard fluorescence imaging systems

Intervention Type: DEVICE

-Member of the operating team will wear the CVG during surgery

Surgery

Intervention Type: PROCEDURE

-Standard of care

Interventions

LS301

-LS301 is a small molecule consisting of a NIR fluorescent dye and an octapeptide that is cyclized through a disulfide bond.

Intervention Type: DRUG

Cancer Vision Goggles and standard fluorescence imaging systems

-Member of the operating team will wear the CVG during surgery

Intervention Type: DEVICE

Surgery

-Standard of care

Intervention Type: PROCEDURE

Other Intervention Names

CVG

Eligibility 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.

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

Sponsors

Samuel Achilefu

OTHER

Sponsor Role: lead

Responsible Party

Samuel Achilefu

Professor & Chair

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Samuel Achilefu, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Deborah Farr, M.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STU-2022-0385

Identifier Type: -

Identifier Source: org_study_id