Breast CancerNCT01837225
ALA-induced Fluorescence Imaging of Breast Cancers Using the Handheld PRODIGI and Eagle Imaging Devices
An observational study of Breast Cancer, run by University Health Network, Toronto at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- Type of treatment
- Pill or oral medicine
- How many people
- 90 participants
- Where
- 2 sitesCanada
- Study dates
- Sep 2010to 31 Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Female patients with breast cancer
- 18 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)
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Enrolling by invitation
Princess Margaret Cancer Centre
Toronto, Ontario, M5G2M9
- Recruiting
Princess Margaret Hospital
Toronto, Ontario, M5T 2M9
Ralph S DaCosta, PhD
Wey L Leong, MD
About this study
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.
Read the 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
- Keywords
- Fluorescence Imaging, Breast Tumor Margins, Real-time Assessment
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2013 (estimated)
- Study startSep 2010
- Primary completion31 Aug 2025 (estimated)
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ralph S DaCosta, PhD, Principal investigator, University Health Network, TorontoWey L Leong, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01837225
- Sponsor's protocol ID
- 10-0633-CE
- Status last verified
- Feb 2024
- First submitted
- 3 Apr 2013
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Aggregate data will be made available through publication
Publications
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.
PubMed 38822389Ottolino-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.
PubMed 34253233
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALA-induced Fluorescence Imaging of Breast Cancers Using the Handheld PRODIGI and Eagle Imaging Devices
- ClinicalTrials.gov ID
- NCT01837225
- Acronym / sponsor ID
- 10-0633-CE
- Conditions
- Breast Cancer
- Keywords
- Fluorescence Imaging, Breast Tumor Margins, Real-time Assessment
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- 31 Aug 2025 (estimated)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 23 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- Female patients with breast cancer
- 18 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
1 secondary outcome
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Derived from this study: PubMed 38822389Gibson 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.
- Derived from this study: PubMed 34253233Ottolino-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.
- Individual participant dataSharing planned: Yes. Aggregate data will be made available through publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralph S DaCosta, PhD principal investigator
University Health Network, Toronto
Wey L Leong, MD principal investigator
University Health Network, Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by University Health Network, Toronto at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ralph S DaCosta, PhD ((416) 581 8645, ralph.dacosta@uhnresearch.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01837225, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.