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Fluorescence Imaging of Carcinoma During Breast Conserving Surgery

Primary Purpose

Breast Neoplasm Female, Breast Cancer

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Aminolevulinic Acid Hydrochloride
Eagle V1.2 Imaging System
Placebo
Sponsored by
SBI ALApharma Canada, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasm Female focused on measuring Breast conserving surgery, Fluorescence Imaging, Intraoperative margin assessment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Female, 18 years or older
  2. Histologically or cytologically confirmed primary breast cancer (includes invasive lobular carcinoma, invasive ductal carcinoma, inflammatory breast cancer, papillary breast cancer, adenoid cystic carcinoma of the breast, mucinous breast cancer, metaplastic breast cancer, cribriform carcinoma and ductal carcinoma in situ, alone or in combination with invasive disease)
  3. Scheduled for a lumpectomy (including bilateral lumpectomy) of a breast malignancy (eligibility for breast conserving surgery/partial mastectomy based on clinical staging using TNM staging system (AJCC Cancer Staging Manual: Breast Cancer, 8th Edition70).
  4. Patient must have normal organ and bone marrow function and be appropriate surgical candidate per site standard of care
  5. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) starting the day entering the study, and for the duration of the study period (until the Week 2 visit)

Exclusion Criteria:

  1. Currently on (neo)adjuvant therapy to treat another cancer
  2. Receiving or intended to receive neoadjuvant therapy to treat the primary breast cancer (including chemotherapy, endocrine therapy and radiotherapy)
  3. Stage 4 cancer, inclusive of metastatic disease
  4. Non-invasive diseases of the breast (includes lobular carcinoma in situ, phyllodes and Paget's disease of the breast)
  5. Patients who have had previous surgery on the involved breast including breast surgeries, mastectomies, breast reconstructions or implants
  6. Patients for whom intraoperative frozen section analysis is planned
  7. Patients who have not recovered from adverse events due an investigational pharmaceutical or diagnostic agents administered more than 30 days prior to their scheduled surgical procedure
  8. History of hypersensitivity to ALA HCl or porphyrins
  9. Known or documented personal or family history of porphyria
  10. Patient has a recording of any parameter as defined below:

    1. Bilirubin: Above upper limit of normal
    2. Aspartate aminotransferase (SGOT): > 2.5 X institutional upper limit of normal
    3. Alanine aminotransferase ( (SGPT): > 2.5 X institutional upper limit of normal
  11. Patient has serum creatinine >1.5 times institutional upper limit of normal, OR calculated creatinine clearance > 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal.
  12. Uncontrolled concurrent illness, that in the opinion of the Investigator would prevent the patient from participation in the study, including but not limited to:

    1. Ongoing or active infection;
    2. Cardiovascular disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia).
  13. Patients who have the following collagen vascular diseases:

    1. Lupus
    2. Scleroderma
  14. Use of an investigational drug within 30 days of their scheduled surgical procedure
  15. Simultaneous use of other potentially phototoxic substances (such as St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing ALA for 24 hours during the perioperative period.
  16. Social or medical situations including uncontrolled psychiatric illnesses that would in the opinion of the Investigator limit compliance with study requirements (e.g. ability to travel for follow-up)
  17. Patients who are pregnant or become pregnant (it is unknown if ALA HCl is teratogenic or has abortifacient effects)
  18. Patients who are breast feeding (there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ALA HCl, breastfeeding should be discontinued if the mother is treated with ALA HCl)
  19. Inability to consent

Sites / Locations

  • Orlando Health, Inc.Recruiting
  • Montefiore Medical CenterRecruiting
  • Aurora St. Luke's Medical CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Standard of Care Arm

PD G 506 A + Fluorescence-Guided Resection Arm

Arm Description

Patients in this arm will receive the placebo orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence-guided resection will not be performed in patients in this arm.

Patients in this arm will receive PD G 506 A orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence imaging performed after SoC BCS is complete will guide the resection of additional tissue.

Outcomes

Primary Outcome Measures

Positive margin conversion rate
Percentage of patients with negative-margins following fluorescence-guided resection (FGR) among patients with positive margins following standard of care (SoC)
Diagnostic performance (Specificity)
Patient-level specificity to identify residual carcinoma
Diagnostic performance (Sensitivity)
Patient-level sensitivity to identify residual carcinoma

Secondary Outcome Measures

Orientation-level diagnostic performance
Orientation-level diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of cancer in the surgical cavity as compared to margin histopathology.
Positive margin conversion rate among all patients
Percentage of patients with at least one histopathology-positive margin following SoC who then have ALL histopathology-negative margins following FGR, among all patients imaged.
Patient-level diagnostic performance
Patient-level sensitivity, specificity, NPV, PPV of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer
Patient-level diagnostic performance of PD G 506 A to detect residual cancer at the end of FGR with modified patient-level definitions
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR (using modified patient-level definitions)
Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC BCS
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC BCS.
Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC with modified patient-level definitions
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC (using modified patient-level definitions).
Patient-level false negative rate of at the end of FGR
Percentage of patients assessed as residual tumor negative at the end of FGR who had positive final margins on histopathology
Patient-level false positive rate
Percentage of patients in whom SOC final margins were carcinoma negative and all FL-driven shave specimens are carcinoma-negative
Patients with carcinoma-negative margins after SoC found to have residual tumor following SoC that was identified with FL imaging
Percentage of patients with histopathology-negative margins at the end of SoC who have at least one orientation that was both FL-positive and histopathology-positive among (1) patients with histopathology negative final margins after SOC and (2) all patients imaged
Patient-level true negative rate at the end of SoC
Percentage of patients with no fluorescence identified at the end of SoC in whom all final margins after SoC are histopathologically confirmed to be negative for carcinoma.
Patient-level diagnostic performance to identify in vivo residual carcinoma after FGR
Patient-level in vivo diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR as compared to the final margin histopathology.
Orientation discordant fluorescence status
Percentage of orientations where in vivo and ex vivo fluorescence assessments are discordant.
Patient-level re-operation rate
Percentage of patients receiving a 2nd surgery on the ipsilateral breast within 1 year of index BCS to remove suspected residual disease.
Patient-level early re-operation rate
Percentage of patients receiving an early 2nd surgery (planned or actual) on the ipsilateral breast related to positive final margins.
Amount of tissue removed with FGR beyond SoC
Weight (mg) of all tissue removed based on SoC and/of FGR
Patient satisfaction with breast
Patient satisfaction with the cosmetic outcome of breast conserving surgery performed based on SoC in combination with PD G 506 A and the Eagle V1.2 Imaging System

Full Information

First Posted
March 22, 2021
Last Updated
August 3, 2023
Sponsor
SBI ALApharma Canada, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04815083
Brief Title
Fluorescence Imaging of Carcinoma During Breast Conserving Surgery
Official Title
A Prospective Multi-center Clinical Study Evaluating the Use of PD G 506 A and the Eagle V1.2 Imaging System for the Visualization of Carcinoma During Breast Conserving Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2021 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SBI ALApharma Canada, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Breast conserving surgery (BCS) is performed on patients with breast cancer to resect and completely remove the cancer while conserving as much of the surrounding healthy tissue as possible. Current methods do not allow surgeons to determine the completeness of surgical resection in real-time. This often results in the need for a second surgical procedure, or in some cases more than two surgical procedures in order to have confidence that all cancer has been removed. This Phase 3 study will evaluate the safety and efficacy of the fluorescent imaging agent PD G 506 A for the real-time visualization of cancer during standard of care breast conserving surgery. PD G 506 A is an investigational drug which is converted in the body into a fluorescent molecule that accumulates in cancer cells. Patients receiving PD G 506 A will undergo standard of care breast conserving surgery followed by fluorescence imaging and removal of any potentially cancerous tissue left behind in the surgical cavity.
Detailed Description
Re-operations due to positive margins following breast conserving surgery (BCS) increase poor cosmesis, complications, discomfort, stress, adjuvant delay, medical costs and risk of local recurrence. Reducing positive margin rates can be achieved through optimizing surgical procedures. This study evaluates a new method for surgeons to visualize carcinoma in real-time, both in the surgical cavity and on the margins of excised specimen(s) during the index BCS procedure. The active ingredient of PD G 506A is aminolevulinic acid hydrochloride (ALA HCl). ALA HCl is a prodrug that is metabolized intracellularly to form the fluorescent molecule protoporphyrin IX (PpIX). The exogenous application of ALA HCl leads to a highly selective accumulation of PpIX in malignant tissues. This Phase 3, 2-part, single-blind [pathologist(s)-blinded] randomized placebo-controlled trial study is designed to evaluate the efficacy and safety of PD G 506 A to aid in the visualization of carcinoma during BCS. The Eagle V1.2 Imaging System will be used in this trial to visualize PpIX fluorescence. Part A is an open-label training phase of the study to optimize workflow and Part B of the study is randomized and single-blind and will serve as the pivotal portion of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasm Female, Breast Cancer
Keywords
Breast conserving surgery, Fluorescence Imaging, Intraoperative margin assessment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
Part A of the study is open-label. All patients in Part A will receive the investigational drug and will undergo standard of care breast conserving surgery (BCS) followed by fluorescence-guided resection. Part B of the study is randomized and placebo controlled; patients will be randomized to receive placebo + standard of care BCS alone or PD G 506 A + SoC BCS followed by fluorescence-guided resection.
Masking
ParticipantOutcomes Assessor
Masking Description
In Part B, the participant and pathologist will be blind to treatment arm allocation for the duration of the study. The surgeon will be blind to treatment arm allocation up until the time that standard of care resection is complete. The blind will be broken during the surgical procedure after the surgeon declares standard of care resection complete.
Allocation
Randomized
Enrollment
370 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care Arm
Arm Type
Placebo Comparator
Arm Description
Patients in this arm will receive the placebo orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence-guided resection will not be performed in patients in this arm.
Arm Title
PD G 506 A + Fluorescence-Guided Resection Arm
Arm Type
Experimental
Arm Description
Patients in this arm will receive PD G 506 A orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence imaging performed after SoC BCS is complete will guide the resection of additional tissue.
Intervention Type
Drug
Intervention Name(s)
Aminolevulinic Acid Hydrochloride
Other Intervention Name(s)
PD G 506 A
Intervention Description
PD G 506 A for oral solution (aminolevulinic acid [ALA] hydrochloride [HCl] granules for oral solution) is administered as a single dose (20 mg/kg body weight) approximately 3 hours (min 2 hours, max 4 hours) prior to anesthesia.
Intervention Type
Device
Intervention Name(s)
Eagle V1.2 Imaging System
Intervention Description
Fluorescence imaging camera and associated accessories used to view and capture fluorescence and white light images and videos of the surgical cavity and excised tissue specimens during the surgical procedure.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral placebo is administered as a single dose approximately 3 hours (min 2 hours, max 4 hours) prior to anesthesia.
Primary Outcome Measure Information:
Title
Positive margin conversion rate
Description
Percentage of patients with negative-margins following fluorescence-guided resection (FGR) among patients with positive margins following standard of care (SoC)
Time Frame
2 weeks
Title
Diagnostic performance (Specificity)
Description
Patient-level specificity to identify residual carcinoma
Time Frame
2 weeks
Title
Diagnostic performance (Sensitivity)
Description
Patient-level sensitivity to identify residual carcinoma
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Orientation-level diagnostic performance
Description
Orientation-level diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of cancer in the surgical cavity as compared to margin histopathology.
Time Frame
2 weeks
Title
Positive margin conversion rate among all patients
Description
Percentage of patients with at least one histopathology-positive margin following SoC who then have ALL histopathology-negative margins following FGR, among all patients imaged.
Time Frame
2 weeks
Title
Patient-level diagnostic performance
Description
Patient-level sensitivity, specificity, NPV, PPV of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer
Time Frame
2 weeks
Title
Patient-level diagnostic performance of PD G 506 A to detect residual cancer at the end of FGR with modified patient-level definitions
Description
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR (using modified patient-level definitions)
Time Frame
2 weeks
Title
Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC BCS
Description
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC BCS.
Time Frame
2 weeks
Title
Patient-level diagnostic performance of PD G 506 A to detect cancer after SoC with modified patient-level definitions
Description
Patient-level sensitivity, specificity, PPV and NPV to determine the presence or absence of cancer in the surgical cavity after SoC (using modified patient-level definitions).
Time Frame
2 weeks
Title
Patient-level false negative rate of at the end of FGR
Description
Percentage of patients assessed as residual tumor negative at the end of FGR who had positive final margins on histopathology
Time Frame
2 weeks
Title
Patient-level false positive rate
Description
Percentage of patients in whom SOC final margins were carcinoma negative and all FL-driven shave specimens are carcinoma-negative
Time Frame
2 weeks
Title
Patients with carcinoma-negative margins after SoC found to have residual tumor following SoC that was identified with FL imaging
Description
Percentage of patients with histopathology-negative margins at the end of SoC who have at least one orientation that was both FL-positive and histopathology-positive among (1) patients with histopathology negative final margins after SOC and (2) all patients imaged
Time Frame
2 weeks
Title
Patient-level true negative rate at the end of SoC
Description
Percentage of patients with no fluorescence identified at the end of SoC in whom all final margins after SoC are histopathologically confirmed to be negative for carcinoma.
Time Frame
2 weeks
Title
Patient-level diagnostic performance to identify in vivo residual carcinoma after FGR
Description
Patient-level in vivo diagnostic performance of PD G 506 A-induced fluorescence to determine the presence or absence of residual cancer in the surgical cavity at the end of FGR as compared to the final margin histopathology.
Time Frame
2 weeks
Title
Orientation discordant fluorescence status
Description
Percentage of orientations where in vivo and ex vivo fluorescence assessments are discordant.
Time Frame
2 weeks
Title
Patient-level re-operation rate
Description
Percentage of patients receiving a 2nd surgery on the ipsilateral breast within 1 year of index BCS to remove suspected residual disease.
Time Frame
1 year
Title
Patient-level early re-operation rate
Description
Percentage of patients receiving an early 2nd surgery (planned or actual) on the ipsilateral breast related to positive final margins.
Time Frame
3 - 6 months
Title
Amount of tissue removed with FGR beyond SoC
Description
Weight (mg) of all tissue removed based on SoC and/of FGR
Time Frame
2 weeks
Title
Patient satisfaction with breast
Description
Patient satisfaction with the cosmetic outcome of breast conserving surgery performed based on SoC in combination with PD G 506 A and the Eagle V1.2 Imaging System
Time Frame
2 weeks, 3-, 6- and 12-months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female, 18 years or older Histologically or cytologically confirmed primary breast cancer (includes invasive lobular carcinoma, invasive ductal carcinoma, inflammatory breast cancer, papillary breast cancer, adenoid cystic carcinoma of the breast, mucinous breast cancer, metaplastic breast cancer, cribriform carcinoma and ductal carcinoma in situ, alone or in combination with invasive disease) Scheduled for a lumpectomy (including bilateral lumpectomy) of a breast malignancy (eligibility for breast conserving surgery/partial mastectomy based on clinical staging using TNM staging system (AJCC Cancer Staging Manual: Breast Cancer, 8th Edition70). Patient must have normal organ and bone marrow function and be appropriate surgical candidate per site standard of care Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) starting the day entering the study, and for the duration of the study period (until the Week 2 visit) Exclusion Criteria: Currently on (neo)adjuvant therapy to treat another cancer Receiving or intended to receive neoadjuvant therapy to treat the primary breast cancer (including chemotherapy, endocrine therapy and radiotherapy) Stage 4 cancer, inclusive of metastatic disease Non-invasive diseases of the breast (includes lobular carcinoma in situ, phyllodes and Paget's disease of the breast) Patients who have had the following procedures performed on the involved breast: Surgery for a benign lesion(s) within 1 year of the BCS date Breast implants inserted within 1 year of the BCS date Breast reduction, surgery for malignant disease or mastectomy (at any time prior to the BCS date) Surgery for a benign lesion(s) or insertion of implants >1 year prior to the BCS date and who have signs of ongoing inflammation, active tissue healing and/or extensive scarring Radiation at any time prior to the BCS date and who have signs of ongoing inflammation, active tissue healing and/or extensive scarring Patients for whom intraoperative frozen section analysis is planned Patients who have not recovered from adverse events due an investigational pharmaceutical or diagnostic agents administered more than 30 days prior to their scheduled surgical procedure History of hypersensitivity to ALA HCl or porphyrins Known or documented personal or family history of porphyria Patient has a recording of any parameter as defined below: Bilirubin: Above upper limit of normal Aspartate aminotransferase (SGOT): > 2.5 X institutional upper limit of normal Alanine aminotransferase ( (SGPT): > 2.5 X institutional upper limit of normal Patient has serum creatinine >1.5 times institutional upper limit of normal, OR calculated creatinine clearance > 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal. Uncontrolled concurrent illness, that in the opinion of the Investigator would prevent the patient from participation in the study, including but not limited to: Ongoing or active infection; Cardiovascular disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia). Patients who have the following collagen vascular diseases: Lupus Scleroderma Use of an investigational drug within 30 days of their scheduled surgical procedure Simultaneous use of other potentially phototoxic substances (such as St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing ALA for 24 hours during the perioperative period. Social or medical situations including uncontrolled psychiatric illnesses that would in the opinion of the Investigator limit compliance with study requirements (e.g. ability to travel for follow-up) Patients who are pregnant or become pregnant (it is unknown if ALA HCl is teratogenic or has abortifacient effects) Patients who are breast feeding (there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ALA HCl, breastfeeding should be discontinued if the mother is treated with ALA HCl) Inability to consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maeve Richmond
Phone
(289) 800-9460
Email
m.richmond@sbi-alapharma.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Jagapreetha Visweswaran
Phone
(289) 800-9408
Email
j.visweswaran@sbi-alapharma.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralph DaCosta, PhD
Organizational Affiliation
SBI ALApharma Canada
Official's Role
Study Director
Facility Information:
Facility Name
Orlando Health, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Durand, RN
Phone
321-843-2026
Email
jennifer.durand@orlandohealth.com
First Name & Middle Initial & Last Name & Degree
Melinda Porter, RN
Phone
321-841-1077
Email
janice.porter@orlandohealth.com
First Name & Middle Initial & Last Name & Degree
Terry P. Mamounas, MD
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Suarez
Phone
718-920-6742
Email
mesuarez@montefiore.org
First Name & Middle Initial & Last Name & Degree
Linda Castellanos
Phone
718-920-7933
Email
lcastellan@montefiore.org
First Name & Middle Initial & Last Name & Degree
Sheldon M. Feldman, MD
Facility Name
Aurora St. Luke's Medical Centre
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Donahoe, RN
Email
Christian.Donahoe@aah.org
First Name & Middle Initial & Last Name & Degree
Nicole Zaremba, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Fluorescence Imaging of Carcinoma During Breast Conserving Surgery

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