Study to Evaluate the Feasibility of 13-C Pyruvate Imaging in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy (LABC)

Breast cancer is the second most common form of cancer in women and the most frequent cause of death. Despite breast screening programs, a substantial number of women are diagnosed with cancers greater than 2 cm in size or locally advanced disease, which is best treated with neoadjuvant chemotherapy (NAC) prior to surgery. Approximately 10% of women diagnosed with breast cancer annually will have locally advanced breast cancer, defined as stage III disease, where the cancer has either spread to regional lymph nodes and/or other tissue in the area of the breast, but not to distant sites. NAC offers the advantages of downstaging the disease, potentially reducing the extent of surgery. Presently, gadolinium enhanced MRI is the standard test used to monitor disease response to chemotherapy, and demonstrates changes in tumour size and extent between pre-NAC and post-NAC. Unfortunately, changes in tumour size may occur late in treatment regimen, thus producing false-negative results on early magnetic resonance imaging (MRI). Therefore, newer imaging techniques beyond anatomical imaging are needed to identify tumours that are unresponsive to chemotherapy and potentially change treatment plan early on to avoid significant morbidity associated with prolonged chemotherapy.

A novel MRI technique utilizing hyperpolarized pyruvate has the potential to detect pathophysiological response early in the treatment regimen and would therefore allow for earlier identification of nonresponders and subsequent early modification of treatment regimens, if necessary.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Hyperpolarized Pyruvate (13C) Injection; Drug: NAC; Other: Coil Testing

Detailed Description

Objectives:

Primary Objective To assess feasibility of of acquiring time resolved, 3D 13C pyruvate MR images of breast cancer requiring neoadjuvant chemotherapy after administration of hyperpolarized 13C pyruvate.

Secondary Objectives

1. To determine the diagnostic accuracy of time resolved, 3D 13C pyruvate MR imaging after administration of hyperpolarized 13C pyruvate for differentiating breast cancer from normal breast parenchyma.
2. To spatially correlate lactate seen on hyperpolarized 13C MR to anatomic imaging with conventional MRI.
3. To assess if hyperpolarized 13C pyruvate MR can differentiate between tumour necrosis versus viable tumour
4. To acquire statistical information to help design, fund, and power future clinical studies with larger patient populations.

Overall Study Design This is a pilot prospective, single-institution study in participants who will receive NAC. Participants will be first informed of the study by personnelle within the patient's circle of care. If the patient expresses interest in participating in the study, the study's Clinical Research Coordinator will approach the patient to provide further information, answer any questions, provide study documentation, as well as to obtain informed consent if agreeable. Clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC) under the supervision of medically trained personnelle.

- Population: A total of 13 participants will be recruited for this study. Prior to the first study research MRI scan, we will scan up to 3 volunteer participants with a known breast malignancy (Group 1). These participants will not have hyperpolarized 13C pyruvate administered. They will be scanned with a 13C phantom in order to test the functionality of the 13C coil.

Subsequently, up to 10 volunteer participants with breast cancer requiring NAC, between 18 and 80 years of age with pathology- and imaging-confirmed breast cancer requiring NAC will be studied (Group 2). Imaging confirmation involves highly suspicious masses on mammography and/or ultrasound. Pathology confirmation involves image-guided core biopsy of the suspicious mass.

• Design: Each participant will receive one research MRI scan on the 3T MRI scanner prior to NAC. This visit will occur separately from the patient's clinical dynamic contrast enhanced (DCE) MRI.
• Scan Timing: The research MRI exam will be scheduled before the initiation of NAC, and within 5 days prior to, or following, the clinical MRI scan.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants of all ethnic groups/ race categories (age: between 18 and 80 years old)
• Radiographic diagnosis and pathologic confirmation of breast cancer
• Undergoing NAC prior to breast-conservation surgery (not applicable to the 3 participants not receiving the injection)
• Estimated survival more than 1 month
• Informed consent
• The participant will also be asked to complete the standard MRI safety screening questionnaire, prior to their research scan and participation in the study.
• Negative pregnancy test for females of child bearing potential
• Aspartate aminotransferase (AST) <31 U/L
• Alanine aminotransferase (ALT) <31 U/L
• Creatinine 44 - 106 umol/L

Exclusion Criteria:

• Contraindication to MRI or intravenous contrast agents
• Women that are pregnant or breastfeeding
• Participants weighing >136 kgs (weight limit for the scanner tables)
• Participants with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices not compatible with MRI.
• Pregnant
• Claustrophobia
• Inability to lie still for 45-60 minutes
• Participants with a high risk factor for nephrogenic systemic fibrosis (NFS), including renal failure on dialysis, heart disease, diabetes, single kidney, hypertension/hypotension, multiple myeloma, peripheral vascular disease, or taking of specific medications (loop diuretics, NSAIDs (within 7 days of research MRI), aminoglycosides, vancomycin, amphotericin B, chemotherapy, or immunosuppressants).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hyperpolarized Pyruvate (13C) Injection; The Participants in the active comparator arm will be injected with study drug Hyperpolarized Pyruvate (13C) Injection at a dose of 0.43/ml/kg. After the injection research, MRI will be done and images evaluated.	Drug: Hyperpolarized Pyruvate (13C) Injection; The new imaging method being tested in this study is called Metabolic MRI, which provides pictures of the metabolism occurring within cancer cells. It also involves injection of a contrast medicine, Hyperpolarized Pyruvate (13C) Injection, into the arm vein. The Participants in the active comparator arm will be injected with study drug Hyperpolarized Pyruvate (13C) Injection at a dose of 0.43/ml/kg.; Other Names: Imaging Agent; Drug: NAC; Participants will be receiving NAC as part of their clinical treatment.; Other Names: Neoadjuvant Chemotherapy
Placebo Comparator: Coil Testing; Participants will receive an MRI with a 1 cm diameter plastic ball that contains 13C-urea that acts as test object. It provides a signal that is used to ensure that the MRI system is functioning properly.	Drug: NAC; Participants will be receiving NAC as part of their clinical treatment.; Other Names: Neoadjuvant Chemotherapy; Other: Coil Testing; Participants will receive an MRI with a 1 cm diameter plastic ball that contains 13C-urea that will act as a test object. The test object provides a signal that will be used to ensure that the MRI system is functioning properly for participants in Group 2 . The plastic ball does not come in contact with you and there are no known risks associated with it.; Other Names: Sentinel tabletop breast imaging coil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time resolved, 3D 13C pyruvate MR images using MRI	Feasibility of of acquiring time resolved, 3D 13C pyruvate MR images of breast cancer requiring neoadjuvant chemotherapy after administration of hyperpolarized 13C pyruvate.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of time resolved, 3D 13C pyruvate MR imaging using visual analysis of MRI images	Diagnostic accuracy of time resolved, 3D 13C pyruvate MR imaging after administration of hyperpolarized 13C pyruvate for differentiating breast cancer from normal breast parenchyma.	6 Months
Lactate Correlation using visual analysis of MRI Images	Correlate lactate seen on hyperpolarized 13C MR to anatomic imaging with conventional MRI.	6 Months
Visual differentiation between tumour necrosis versus viable tumour	Differentiate between tumour necrosis versus viable tumour with Hyperpolarized 13C pyruvate MRI	6 Months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): March 23, 2023
• Study Completion (Actual): March 23, 2023

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 254-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes