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

NCT03121989 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 254-2015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Accuracy of time resolved, 3D 13C pyruvate MR imaging using visual analysis of MRI images

  6 Months

• Lactate Correlation using visual analysis of MRI Images

  6 Months

• Visual differentiation between tumour necrosis versus viable tumour

  6 Months

Study Arms (2)

Hyperpolarized Pyruvate (13C) Injection

ACTIVE COMPARATOR

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; Drug: NAC

Coil Testing

PLACEBO COMPARATOR

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.

Other: Coil Testing; Drug: NAC

Interventions

Hyperpolarized Pyruvate (13C) Injection DRUG

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.

Also known as: Imaging Agent

Hyperpolarized Pyruvate (13C) Injection

Coil Testing OTHER

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.

Also known as: Sentinel tabletop breast imaging coil

Coil Testing

NAC DRUG

Participants will be receiving NAC as part of their clinical treatment.

Also known as: Neoadjuvant Chemotherapy

Coil Testing; Hyperpolarized Pyruvate (13C) Injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Injections; acetyl-glycyl-asparagyl-glutaminyl-glutamyl-glutaminyl-valyl-seryl-prolyl-leucyl-threonyl-leucyl-leucyl-lysyl-lysyl-tryptophyl-cysteinyl-Alexa Fluoro 680 C2C2-maleimide conjugate; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Combined Modality Therapy

Study Officials

• Charles Cunningham, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 13 participants will be recruited for this study. Prior to the first study research MRI scan, 3 volunteer participants will be scanned 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.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: April 20, 2017
• Study Start: November 21, 2017
• Primary Completion: March 23, 2023
• Study Completion: March 23, 2023
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)