The LightPath® and 68Ga-RM2 in Breast Cancer Study

Study Overview
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Brief Summary
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This study is a prospective, open-label study to examine the performance of the LightPath® Imaging System using the PET tracer 68Ga-RM2 in patients scheduled for and/or undergoing wide local excision (WLE) with or without sentinel lymph node biopsy (SLNB) or complete axillary lymph node dissection(cALND) for breast cancer with an ER-positive invasive primary cancer. The study consists of 3 sequential groups: Group 1 (N=20 patients): Torso, i.e. base of skull to thighs, PET/CT imaging and axillary gamma probe measurements (using a collimator) of 68Ga-RM2 to: determine the optimal scan time-window post-injection; to extrapolate the optimal dose for resolution against axillary background signal on gamma probe measurements (first 6 patients); and the value of 68Ga-RM2 PET/CT imaging for breast cancer staging (all 20 patients). Group 2 (N=10 patients): Intraoperative LightPath® imaging with 68Ga-RM2 to familiarise site with procedure and interpretation of intraoperative scans,validate the dose and timings determined from Group 1, and optimise LightPath® Imaging parameters such as acquisition resolution and duration. Group 2 scans will acquire LightPath® images of both intact and incised cancer specimens for post-operative standardised, controlled assessment. Group 2 will use the optimal scan time-window and 68Ga-RM2 activity extrapolated from at least the first 6 patients in Group 1. The dose of 68Ga-RM2 will be determined to optimise the intra-operative imaging and axillary gamma probe measurements. Group 3 (N=50 patients): Intraoperative LightPath® imaging with 68Ga-RM2 to measure agreement between LightPath® images and post-operative histopathology. Group 3 scans will acquire LightPath® images of intact and incised cancer specimens for post-operative standardised, controlled assessment. Group 3 will use the optimal scan time-window and 68Ga-RM2 activity extrapolated from the first 6 patients in Group 1 with the optimised imaging parameters, and dose developed from Group 2. The intraoperative LightPath® Images will be used to inform the surgeons about detectable residual cancer in an attempt to achieve better guided cancer surgery and complete tumour excision with clear WLE resection margins The study site will use the local criteria considered standard of care to guide decisions to act on positive margins. Lightpoint Medical will provide guidance to act on LightPath® Images in the Instructions forUse (IFU). It will be at the Investigator's discretion to choose whether to act based upon the intraoperative LightPath® Images. In Group 3,the resection margin status of the WLE specimen, cavity shavings (if any) and the metastatic status of axillary (sentinel) lymph nodes as measured with the LightPath® Imaging System will be compared with histopathology results. A positive margin on histology will be defined as Invasive carcinoma: positive: ink on tumour; close: <1mm; negative ≥1mm Ductal carcinoma in situ (DCIS)or pleomorphic lobular carcinoma in situ (LCIS) (if present): positive: ink on tumour; close: <2mm; negative ≥2mm.

Official Title
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Evaluation of the LightPath® Imaging System and the PET Tracer 68Ga-RM2 in Wide Local Excision (WLE) for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Combination Product: LightPath® Imaging System and 68Ga-RM2
* Drug: 68Ga-RM2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have signed an informed consent form prior to any study related activity Subjects who are able to give voluntary, written informed consent to participate in this study. Subjects who are able to understand this study and are willing to complete all the study assessments Female subjects ≥18 years of age with a diagnosis of ER-positive invasive breast cancer. ER-positivity is defined as an Allred score of 3 or more on immunohistochemical analysis. Female subjects of childbearing age must have a negative pregnancy test (by Beta HCG qualitative analysis), or must have had a history of a surgical sterilisation, or must give history of no menses in the past twelve months Groups 2 and 3: Subjects scheduled for WLE +/-SLNB or ALND Exclusion Criteria: Subjects who have had surgery in the operated breast in the past 12months Subjects who have had radiotherapy in the operated breast Subjects who have had neoadjuvant systemic therapy Subjects who have had systemic chemotherapy or investigational therapy in the past two years Subjects who are pregnant or lactating Subjects who have a known hypersensitivity to 68Ga, bombesin analogues, or GRPR-antagonists Subjects who have an existing medical condition that would compromise their participation in the study•Subjects with a current or active history of other known cancerin the opinion of the Investigator

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3-Group Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>Patient will receive an IV injection of up to 200MBq 68Ga-RM2. Each patient will have torso PET/CT imaging at 2 timepoints. Alternate patients will have imaging at 1 and 2h post-injection then the next patientat 1 and 3h post-injection, with axillary gamma probe measurements (using a collimator) of 68Ga-RM2 at the same time points. | Drug: 68Ga-RM2<br>* Radiopharmaceutical: 68Ga-RM2 is an investigational Positron Emission Tomography (PET)/ Computed Tomography (CT) radiopharmaceutical.<br>|
| Experimental: Group 2<br>WLE will be performed as per standard of care but will also include Intraoperative LightPath® Imaging with 68Ga-RM2. Group 2 scans will acquire LightPath® images of both intact and incised cancer specimens with varying parameters to optimise imaging. | Combination Product: LightPath® Imaging System and 68Ga-RM2<br>* Imaging System:The LightPath® Imaging System is an in vitro diagnostic device which has CE mark in Europe, in line with In Vitro Diagnostic Medical Devices 98/79/EC (post-marketing study). Radiopharmaceutical: 68Ga-RM2 is an investigational Positron Emission Tomography (PET)/ Computed Tomography (CT) radiopharmaceutical.<br>|
| Experimental: Group 3<br>WLE will be performed as per standard of care but will also include Intraoperative LightPath® Imaging with 68Ga-RM2. Group 3 scans will acquire LightPath® images of intact and incised cancer specimens using a final and consistent imaging procedure. | Combination Product: LightPath® Imaging System and 68Ga-RM2<br>* Imaging System:The LightPath® Imaging System is an in vitro diagnostic device which has CE mark in Europe, in line with In Vitro Diagnostic Medical Devices 98/79/EC (post-marketing study). Radiopharmaceutical: 68Ga-RM2 is an investigational Positron Emission Tomography (PET)/ Computed Tomography (CT) radiopharmaceutical.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of LightPath® Imaging System | Agreement between margin status determined by LightPath® Imaging and post-operative histopathology (Group 3) | up to 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal scan time-window for 68Ga-RM2 PET/CT imaging | Group 1 only | 1 year | 
| Gamma probe measurements (collimated) in the axilla to determine optimal 68Ga-RM2 activity | Group 1 only | 1 year | 
| Value of 68Ga-RM2 PET/CT imaging for breast cancer staging | Group 1 only | 1 year | 
| Radiation dosimetry measurements for the staff | Group 1 only | 1 year | 
| Optimal device settings, tracer dose, and working procedures | Group 2 only | up to 2 years | 
| Inter-rater agreement in post-operative standardised, controlled assessments of LightPath® Images | Group 3 only | up to 5 year | 
| MDT decision to re-operate at index location | Group 3 only | up to 5 year | 
| Weight of primary lump and lump plus shavings | Groups 2 and 3 only | up to 5 year | 
| Radiation dosimetry for operating room and recovery area staff | Groups 2 and 3 only | up to 5 year |