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

NCT01837225 | Recruiting

• 1 other identifier: 10-0633-CE
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

Keywords

Fluorescence Imaging; Breast Tumor Margins; Real-time Assessment

Outcome Measures

Primary Outcomes (1)

• The sensitivities and specificities for the two (oral) doses of 5-ALA (15 mg/kg and 30 mg/kg) and control (0 mg/kg ALA) in differentiating cancer/normal tissue.

  The sensitivity and specificity of fluorescence imaging for differentiating cancer from normal tissue in the breast will be evaluated by tissue histopathology and compared to standard white-light imaging. The sensitivities and specificities for auto-fluorescence (Cohort 1: 0 mg/kg 5-ALA) will be compared to the sensitivities and specificities of the two doses of 5-ALA (Cohort 2: 15mg/kg and Cohort 3: 30mg/kg). In addition, the sensitivities and specificities between the two 5-ALA dosing cohorts will be compared.

  The fluorescence and white-light images will be evaluated and compared to histopathology within an average of 2 months after the surgery. The sensitivities and specificities will be calculated within 4 months of achieving a full dataset (45 patients).

Secondary Outcomes (1)

• A catalogue of the fluorescence signatures associated with the major tissue biological components comprising the breast (e.g. adipose, connective, etc.).

  The fluorescent signatures will be compared to biological components within an average of 2 months after each surgery. The fluorescence catalogue will be created within approximately 4 months of achieving a full dataset (45 patients).

Study Arms (4)

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.

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.

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.

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will be conducted at the Princess Margaret Hospital in Toronto, Canada. Patients undergoing lumpectomy or mastectomy procedures to remove breast tumours will be recruited to participate.

You may qualify if:

• Female patients with breast cancer
• years or older
• Have consented for their standard surgeries for primary invasive breast cancers, with or without auxiliary procedure.
• Have existing biopsies banked at the hospital (for ALA patients)

You may not qualify if:

• Pre-operative therapy (including chemotherapy, endocrine therapy and radiotherapy)
• Inability to consent
• Prior history of photosensitivity, liver disease, or recurrent disease
• Pregnancy
• Absence of in-house core biopsy in tissue bank

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

ENROLLING BY INVITATION

Princess Margaret Hospital

Toronto, Ontario, M5T 2M9, Canada

RECRUITING

Related Publications (2)

• 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.

  PMID: 38822389 DERIVED

• 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.

  PMID: 34253233 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Punch biopsies of healthy and cancerous breast tissue will be acquired from the surgical bed and from the ex-vivo samples.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Ralph S DaCosta, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Wey L Leong, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ralph S DaCosta, PhD

CONTACT

(416) 581 8645; ralph.dacosta@uhnresearch.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 23, 2013
• Study Start: September 1, 2010
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: February 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

CA (2)