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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Breast Neoplasm Female
- Sponsor
- SBI ALApharma Canada, Inc.
- Enrollment
- 57
- Locations
- 7
- Primary Endpoint
- Positive Margin Conversion Rate
- Status
- Terminated
- Last Updated
- 8 months ago
Overview
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.
Investigators
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
Arms & Interventions
Standard of Care Arm
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.
Intervention: Placebo
PD G 506 A + Fluorescence-Guided Resection 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.
Intervention: Aminolevulinic Acid Hydrochloride
PD G 506 A + Fluorescence-Guided Resection 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.
Intervention: Eagle V1.2 Imaging System
Outcomes
Primary Outcomes
Positive Margin Conversion Rate
Time Frame: 2 weeks
Percentage of patients with negative-margins following fluorescence-guided resection (FGR) among patients all patients imaged
Diagnostic Performance (Specificity)
Time Frame: 2 weeks
Patient-level specificity to identify residual carcinoma
Diagnostic Performance (Sensitivity)
Time Frame: 2 weeks
Patient-level sensitivity to identify residual carcinoma
Secondary Outcomes
- Orientation-level Diagnostic Performance(2 weeks)
- Positive Margin Conversion Rate Among All Patients(2 weeks)
- Patient-level Diagnostic Performance(2 weeks)
- Patient-level Diagnostic Performance of PD G 506 A to Detect Residual Cancer at the End of FGR With Modified Patient-level Definitions(2 weeks)
- Patient-level Diagnostic Performance of PD G 506 A to Detect Cancer After SoC BCS(2 weeks)
- Patient-level Diagnostic Performance of PD G 506 A to Detect Cancer After SoC With Modified Patient-level Definitions(2 weeks)
- Patient-level False Negative Rate of at the End of FGR(2 weeks)
- Patient-level False Positive Rate(2 weeks)
- Patients With Carcinoma-negative Margins After SoC Found to Have Residual Tumor Following SoC That Was Identified With FL Imaging(2 weeks)
- Patient-level True Negative Rate at the End of SoC(2 weeks)
- Patient-level Diagnostic Performance to Identify in Vivo Residual Carcinoma After FGR(2 weeks)
- Orientation Discordant Fluorescence Status(2 weeks)
- Patient-level Re-operation Rate(1 year)
- Patient-level Early Re-operation Rate(3 - 6 months)
- Amount of Tissue Removed With FGR Beyond SoC(3 - 6 months)
- Patient Satisfaction With Breast(2 weeks, 3-, 6- and 12-months)