Three-Dimensional Ultrasound and Spectroscopy as Early Indicators of Breast Cancer Response to Neoadjuvant Treatment

Investigation of Three-Dimensional Ultrasound and Spectroscopy as Early Indicators of Breast Cancer Response to Neoadjuvant Treatment

The purpose of the study is to test the hypothesis that ultrasound imaging and spectroscopy may be used as a predictive marker of advanced tumour response to neoadjuvant treatment consisting of chemotherapy or concurrent chemotherapy-radiotherapy. The main goal is to select the best ultrasound spectroscopy parameter and vascular-distribution index to use as an early predictor of pathological complete or partial response as a primary endpoint and tumour size decrease as a secondary endpoint.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Ultrasound imaging 3D and Spectroscopy

Detailed Description

This project is an early validation study in human subjects that will use three-dimensional ultrasound imaging and spectroscopy to monitor cell death occurring at various time points during a patient's treatment for advanced breast cancer. Standard neoadjuvant treatments for breast cancer consisting of combined chemotherapy and radiotherapy will be used in patients. Reponses will be followed with ultrasound imaging and spectroscopy at regular predetermined time-points. The research is exploratory since upon data analysis it will examine the use of different ultrasound backscatter parameters as potential markers of cell death and correlate these with changes in tumour size and complete pathological response.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Gregory J Czarnota, PhD, MD; Phone Number: (416) 480-5329; Email: Gregory.Czarnota@sunnybrook.ca

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men and women and members of all races and ethnic groups who will receive standard Neoadjuvant treatment for Breast Cancer.

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed breast carcinoma, stage I-IV, which has not been treated with any first-line therapy and will be treated with neoadjuvant chemotherapy or neoadjuvant combined chemo-radiotherapy.
2. Disease must be measurable by ultrasound, or MRI performed within 28 days prior to treatment.
3. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1.
4. Life expectancy of at least 6 months.

5. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to dosing:

   (i) hemoglobin >90 mg/dL (ii) leukocytes >3,000/mL (iii) absolute neutrophil count >1,500/mL (iv) platelets >100,000/mL (v) total bilirubin within normal institutional limits (vi) AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal (vii) creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional upper limit of normal.

6. Patients should have the ability to understand and the willingness to sign a written informed consent document. Signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

1. Chemotherapy, radiotherapy, or major surgery within 4 weeks prior to registering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to registration.
2. Receiving any other investigational agents.
3. Known brain metastases.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition.

5. Contraindications to radiotherapy such as but not limited to:

   (i) previous radiotherapy to an involved area (ii) active collagen vascular disease (iii) genetic diseases associated with hyper-radiosensitivity.

6. Any clinically serious infections requiring systemic anti-bacterial, antifungal or antiviral therapy.
7. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia.
8. Psychiatric illness/social situations that would limit compliance with study requirements.
9. History of active ongoing seizure disorder.
10. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
11. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard neoadjuvant treatments; Patients will be assessed using ultrasound imaging 3D and spectroscopy at the following intervals: once immediately prior to commencing neoadjuvant treatment. Once treatment begins, patients will be imaged at weeks 2, 4, 8, 12 and then prior to their surgery.	Device: Ultrasound imaging 3D and Spectroscopy; Ultrasound imaging and spectroscopy will consist of collecting three dimensional data. Regions of interest in each of the tumour images and in the adjacent normal tissue will be selected for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasound imaging and spectroscopy as a predictive marker of early predictor of complete pathological response.	The primary endpoint of this study will be to correlate changes in ultrasound backscatter parameters obtained throughout the course of treatment with complete or partial pathological response.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Examine the change in tumour size over the course of treatment and correlating it to changes in ultrasound backscatter parameters.	Tumour size will be measured using conventional B-mode ultrasound imaging. Both the tumour's maximum dimensions length, width, and height in cm will be considered.	Up to 5 years
To Examine the change in tumour Volumen over the course of treatment and correlating it to changes in ultrasound backscatter parameters.	The Volumen of the tumor will be measured by conventional ultrasound in B mode. The volume of the tumor in cm3 will be considered.	Up to 5 years

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Gregory J Czarnota, PhD, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 20, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Spectroscopy; Neoadjuvant Chemotherapy; Three-Dimensional Ultrasound
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 5552

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: No
• Studies a U.S. FDA-regulated device product: No