ALA-induced Fluorescence Imaging of Breast Cancers Using the Handheld PRODIGI and Eagle Imaging Devices

NCT ID: NCT01837225

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2025-08-31

Brief Summary

Breast cancer is the most commonly occurring cancer in women. Currently, breast conservation surgery (BCS) is the treatment most often prescribed. BCS involves removing the tumor while conserving the greatest amount of healthy breast tissue. Under standard white light, tumor borders are difficult for the surgeons to visualize. Therefore, between 30-70% of patients require a second operation to remove remaining cancerous tissue that wasn't detected during the initial surgery. Thus, there is an urgent clinical need for a new imaging tool that improves tumor visualization during the first surgery.

PRODIGI, a new hand-held optical imaging device, uses a safe violet-blue light to detect fluorescence signals in the tissue. Different tissues are associated with specific fluorescent colors and therefore the device can be used to differentiate between tumor and healthy breast tissue. Based on previous clinical data, PRODIGI can distinguish some tumors from normal tissues, but is not specific enough to detect a difference across all breast tumor types.

The fluorescent contrast drug 5-aminolevulinic acid (5-ALA) accumulates in tumors naturally and previous research has shown that 5-ALA increases tumor-normal tissue fluorescence contrast. In this observational clinical study, PRODIGI and 5-ALA will be used to visualize tumor borders during BCS. 5-ALA induced fluorescent images from the surgical sample and the surgical bed obtained by PRODIGI will be compared retrospectively with the images taken under standard white light and/or autofluorescence. The technology's ability to accurately identify tumor borders better than conventional practice will be confirmed by tissue pathology.

Detailed Description

The investigators hypothesize that 5-ALA will selectively increase breast tumor-to-normal fluorescent contrast and therefore increase tumor margin delineation using the PRODIGI device compared to standard white light or autofluorescence visualization. The goal of this observational study is to use intraoperative fluorescence imaging across all three patient cohorts (control, 15mg/kg 5-ALA, 30mg/kg 5-ALA) to determine if there is an increase in tumor-specific fluorescence contrast, and to select the optimum 5-ALA contrast agent dose. All patients across each cohort will receive conventional BCS and care independent of contrast agent dose. Data from this preliminary study will be used to guide the design of future statistically powered randomized controlled trials involving PRODIGI and 5-ALA. However, at this early stage our initial aim is to develop a baseline understanding of the 5-ALA fluorescent signatures in normal and tumor breast tissues in the surgical setting.

This technology has the potential to guide surgeons during BCS and reduce the re-incision rates by ensuring that the surgeons can properly identify tumor from normal tissue during surgery. If successful, this new fluorescence imaging technology may improve patient outcomes by reducing the likelihood of cancer recurrence, accelerating the recovery process and decreasing healthcare costs by eliminating the need for a second surgery.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Control

Patients in the control arm will not receive the fluorescent contrast agent (5-ALA); however, intraoperative fluorescence imaging will still be performed. Patients will receive conventional breast conservation surgery and care independent of the contrast agent dose they receive.

No interventions assigned to this group

Low Dose Contrast Agent

Patients in the low dose arm will receive 15 mg/kg 5-ALA fluorescent contrast agent administered orally 3 hours prior to intraoperative fluorescence imaging. Patients will receive conventional breast conservation surgery and care independent of the contrast agent dose they receive.

No interventions assigned to this group

High Dose Contrast Agent

Patients in the high dose arm will receive 30 mg/kg 5-ALA fluorescent contrast agent administered orally 3 hours prior to intraoperative fluorescence imaging. Patients will receive conventional breast conservation surgery and care independent of the contrast agent dose they receive.

No interventions assigned to this group

Intermediate Dose Contrast Agent

Patients in the intermediate dose arm will receive 20 mg/kg 5-ALA fluorescent contrast agent administered orally 3 hours prior to intraoperative fluorescence imaging. Patients will receive conventional breast conservation surgery and care independent of the contrast agent dose they receive.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Female patients with breast cancer

2. 18 years or older

3. Have consented for their standard surgeries for primary invasive breast cancers, with or without auxiliary procedure.

4. Have existing biopsies banked at the hospital (for ALA patients)

Exclusion Criteria

1. Pre-operative therapy (including chemotherapy, endocrine therapy and radiotherapy)

2. Inability to consent

3. Prior history of photosensitivity, liver disease, or recurrent disease

4. Pregnancy

5. Absence of in-house core biopsy in tissue bank

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

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph S DaCosta, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Wey L Leong, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status: ENROLLING_BY_INVITATION

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Ralph S DaCosta, PhD

Role: CONTACT

ralph.dacosta@uhnresearch.ca

(416) 581 8645

References

Gibson C, Wang SC, Phoon A, Thalanki Anantha N, Ottolino-Perry K, Petropoulos S, Qureshi Z, Subramanian V, Shahid A, O'Brien C, Carcone S, Chung S, Tsui T, Son V, Sukhram M, Meng F, Done SJ, Easson AM, Cil T, Reedijk M, Leong WL, DaCosta RS. A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid. BMC Biomed Eng. 2024 Jun 1;6(1):5. doi: 10.1186/s42490-024-00079-9.

Reference Type: DERIVED

PMID: 38822389 (View on PubMed)

Ottolino-Perry K, Shahid A, DeLuca S, Son V, Sukhram M, Meng F, Liu ZA, Rapic S, Anantha NT, Wang SC, Chamma E, Gibson C, Medeiros PJ, Majeed S, Chu A, Wignall O, Pizzolato A, Rosen CF, Teene LL, Starr-Dunham D, Kulbatski I, Panzarella T, Done SJ, Easson AM, Leong WL, DaCosta RS. Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial. Breast Cancer Res. 2021 Jul 12;23(1):72. doi: 10.1186/s13058-021-01442-7.

Reference Type: DERIVED

PMID: 34253233 (View on PubMed)

Other Identifiers

10-0633-CE

Identifier Type: -

Identifier Source: org_study_id