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ALA-induced Fluorescence Imaging of Breast Cancers Using the Handheld PRODIGI Imaging Device

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ClinicalTrials.gov Identifier: NCT01837225
Recruitment Status : Completed
First Posted : April 23, 2013
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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.


Condition or disease
Breast Cancer

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.


Study Type : Observational
Actual Enrollment : 54 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ALA-induced Fluorescence Imaging of Breast Cancers Using the Handheld PRODIGI Imaging Device
Study Start Date : September 2010
Actual Primary Completion Date : September 2018
Actual Study Completion Date : October 2018

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Group/Cohort
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.



Primary Outcome Measures :
  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. [ Time Frame: 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). ]
    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.


Secondary Outcome Measures :
  1. A catalogue of the fluorescence signatures associated with the major tissue biological components comprising the breast (e.g. adipose, connective, etc.). [ Time Frame: 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). ]
    The fluorescent signatures from punch biopsies taken from the tumour and in normal tissue will be determined using fluorescence point spectroscopy. The biological components of the corresponding punch biopsies will be determined by tissue histopathology. The fluorescence signatures of the different types of tissue (adipose, connective, etc.) will be correlated for all punch biopsies taken as part of the study.


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01837225


Locations
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G2M9
Princess Margaret Hospital
Toronto, Ontario, Canada, M5T 2M9
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Ralph S DaCosta, PhD University Health Network, Toronto
Principal Investigator: Wey L Leong, MD University Health Network, Toronto

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01837225     History of Changes
Other Study ID Numbers: 10-0633-CE
First Posted: April 23, 2013    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Aggregate data will be made available through publication

Keywords provided by University Health Network, Toronto:
Fluorescence Imaging
Breast Tumor Margins
Real-time Assessment

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases