LS301-IT in Partial Mastectomy and Sentinel Lymph Node Biopsy (SLNB) for DCIS or Stage I-II Primary Invasive Breast Cancer

Study Overview
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Brief Summary
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The aim of this Phase 1b/2 study is to investigate the safety, efficacy, and pharmacokinetics (PK) of a single dose of LS301-IT, a novel fluorescence imaging agent developed by Integro Theranostics (IT), administered by intravenous (IV) injection in female patients undergoing partial mastectomy for DCIS (whether or not undergoing planned SLNB) or Stage I-II primary invasive breast cancer undergoing SLNB. Safety is the primary objective of this study, followed by efficacy that will be assessed from fluorescence imaging observations and data.

Detailed Description
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This is a Phase 1b/Phase 2, open-label study to investigate the use of LS301-IT (investigational medicinal product [IMP]), a fluorescence imaging agent used for visualization of tumor margins and SLNs in female patients with DCIS or Stage I-II, primary invasive carcinoma of the breast, for which the patient's primary surgical treatment is partial mastectomy. Eligible patients will be enrolled into either: Phase 1b (Period 1): dose finding (escalation/de-escalation), and dose timing adjustment; Phase 2a (Period 2): expanded sample size based on acceptable dosing regimen, that being the dose level(s) and time interval between LS301-IT injection and surgery, determined in Period 1; or Period 2b (Period 3): allow surgeon to make additional surgical decisions based on fluorescence imaging findings during surgery (Period 3 will not be opened until results are available from Periods 1 and 2 and further FDA consultation is obtained).

Official Title
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An Open-label, Single-arm, Phase 1b/2 Study to Investigate the Safety, Efficacy and Pharmacokinetics of LS301-IT in Female Patients Undergoing Partial Mastectomy and Sentinel Lymph Node Biopsy (SLNB) for Ductal Carcinoma in Situ (DCIS) or Stage I-II Primary Invasive Breast Cancer

Conditions
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Breast Cancer, DCIS, Invasive Duct Carcinoma of Breast

Intervention / Treatment
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* Drug: LS301-IT 0.025 mg/kg
* Drug: LS301-IT 0.05 mg/kg
* Drug: LS301-IT 0.075 mg/kg
* Drug: LS301-IT 0.1 mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DCIS (whether or not undergoing planned SLNB) or patients with Stage I-II, primary invasive carcinoma of the breast undergoing SLNB for which the patient's primary surgical treatment is single breast partial mastectomy. ECOG performance status of 0 to 2 Exclusion Criteria: Contraindications for surgery. Simultaneous bilateral lumpectomies and bilateral partial mastectomies. History of drug-related anaphylactic reactions, including those attributed to indocyanine green (ICG) or other agents used in the study Prior chemotherapy, endocrine therapy, or biologic therapy for current clinically or biopsy proven breast cancer for Period 1. Open surgery in the ipsilateral breast within a period of 1 year before administration of LS301-IT. History of radiation therapy to the chest. The lymphatic imaging agent ICG cannot be used prior to the partial mastectomy and SLNB procedures on the day of surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LS301-IT<br>LS301-IT will be adminstered by IV injection | Drug: LS301-IT 0.025 mg/kg<br>* The dose of LS301-IT planned to be administered to the first cohort of patients is 0.025 mg/kg. Depending on the results the dose for subsequent cohorts will be increased to 0.05, 0.075, and 0.1 mg/kg; the dose may also be decreased (by 50% as necessary). The optimal dose determined in Periods 1 and 2 will be administered to patients in Period 3.<br>Drug: LS301-IT 0.05 mg/kg<br>* Depending on the results the dose for subsequent cohorts will be increased to 0.05, 0.075, and 0.1 mg/kg; the dose may also be decreased. The optimal dose determined in Periods 1 and 2 will be administered to patients in Period 3.<br>Drug: LS301-IT 0.075 mg/kg<br>* Depending on the results the dose for subsequent cohorts will be increased to 0.05, 0.075, and 0.1 mg/kg; the dose may also be decreased. The optimal dose determined in Periods 1 and 2 will be administered to patients in Period 3.<br>Drug: LS301-IT 0.1 mg/kg<br>* Depending on the results the dose for subsequent cohorts will be increased to 0.05, 0.075, and 0.1 mg/kg; the dose may also be decreased. The optimal dose determined in Periods 1 and 2 will be administered to patients in Period 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with treatment-related adverse events | 30 days | 
| Pharmacodynamics | Tumor to non-tumor ratio fluorescence response | during surgery | 
| Pharmacodynamics | Surgeon's assessment using a semi-quantitative scoring system of fluorescence compared with intraoperative and postoperative pathology assessments. | During surgery | 
| Cmax | maximum observed plasma concentration main metabolite in plasma. | 24 hours | 
| AUCinf | area under the plasma concentration time curve from time 0 extrapolated to infinite time | 24 hours | 
| AUClast | area under the plasma concentration-time curve from time 0 to the last quantifiable plasma concentration | 24 hours | 
| Tmax | time to reach maximal plasma concentration (Tmax) | 24 hours | 
| t1/2 | elimination/apparent terminal elimination half life | 24 hours |