Use of Quantitative Ultrasound to Guide Adaptive Chemotherapy Among Women With Breast Cancer

A Phase II Study of Quantitative Ultrasound to Guide Adaptive Chemotherapy Among Women With Locally Advanced Breast Cancer (LABC)

The primary objective of this study is to assess the feasibility of randomizing breast cancer patients to quantitative ultrasound to guide adaptive Neoadjuvant Chemotherapy as compared to standard clinical monitoring and therapy. The Investigators have previously demonstrated that high-frequency ultrasound and spectroscopy, and recently conventional-frequency ultrasound and spectroscopy may be used to detect cell death in vitro, in situ and in vivo. The method can detect different forms of cell death and has been demonstrated to be sensitive to apoptotic, necrotic and mitotic cell death. By detecting cell death early in a treatment on the order of hours to days, rather than traditional anatomical assessments that take place weeks to months after the completion of therapy, ineffective therapies could be switched to more efficacious treatments or aggressive salvage therapy which has shown to already benefit patients. The overarching goal of this research is to transform the delivery of neoadjuvant chemotherapy using quantitative ultrasound (QUS), which is non-invasive, inexpensive and portable.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Quantitative ultrasound to guide adaptive chemotherapy

Detailed Description

This study phase II will demonstrate the use of quantitative ultrasound to guide adaptive chemotherapy for patients with breast cancer. The primary endpoint will be measurement of improved response rate locally. This trial will enroll 240 randomized breast cancer patients to be assess with quantitative ultrasound to guide adaptive neoadjuvant chemotherapy as compared to standard clinical monitoring and therapy. We will evaluate the safety of its use and expect equivalence in this small patient population. This will allow for more accurate estimation of a needed sample size for a phase III superiority trial.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gregory J Czarnota, PhD, MD; Phone Number: (416) 480-6128; Email: gregory.czarnota@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Gregory J Czarnota, PhD, MD; Phone Number: (416) 480-6128; Email: gregory.czarnota@sunnybrook.ca
      • Principal Investigator: Maureen E Trudeau, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women ≥ 18 years of age
2. Diagnosis of breast cancer with a primary tumour >2cm in size
3. With conditions meeting criteria for chemotherapy administration
4. Normal hematological blood counts (hemoglobin ≥ 100 g/l, platelet count ≥ 100 x 109, absolute neutrophil count ≥ 2.0 x109 cells per L)
5. Creatinine ≤175 µmol/L
6. Liver enzymes (AST and ALT) ≤ 1.5 times upper limit of normal
7. Cardiac function (left ventricular ejection fraction) ≥55%
8. Eligible for neoadjuvant chemotherapy.

Exclusion Criteria:

1. Inflammatory breast cancer
2. Contraindications to neoadjuvant treatment including pregnancy or lactation
3. Past medical history of connective tissue disease
4. Past history of dermatologic disease involving the breast
5. Eastern Cooperative Group Status (ECOG) ≥3
6. No peripheral neuropathy of a severity of grade ≥2
7. Evidence of distant metastatic disease
8. Known sensitivity to components present in ultrasound gel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Neoadjuvant Chemotherapy Monitoring; Patients who will be randomized to the control arm with Standard Neoadjuvant Chemotherapy Monitoring will receive Phase I chemotherapy consisting of anthracycline-based treatment followed by Phase II chemotherapy consisting of taxane-based treatment. Patients will be imaged but no modifications to treatment will occur in this trial arm depending on response by quantitative ultrasound.
Experimental: Adaptive Chemotherapy Monitoring; Patients who will be randomized to the experimental arm Adaptive Chemotherapy Monitoring and demonstrate Response (+) will continue until standard chemotherapy is completed. For patients who do not demonstrate response after 4 weeks of chemotherapy, an early switch to the second phase of chemotherapy could occur (Phase II/Taxane) At the discretion of the treating medical oncologist. Patients will undergo Quantitative Ultrasound on the following time points: Pre-treatment, Weeks 1, 4, 8, 12 and Pre-Operatively. These QUS time points correspond to the following chemotherapy times.	Device: Quantitative ultrasound to guide adaptive chemotherapy; Quantitative ultrasound results will be used to measure chemotherapy response and guide an adaptive chemotherapy strategy for patients who are found to be nonresponders to their chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring the rate of treatment response between the treatment groups	To assess the feasibility of randomizing breast cancer patients to quantitative ultrasound to guide adaptive neoadjuvant chemotherapy as compared to standard clinical monitoring and therapy.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical efficacy of quantitative ultrasound	Sensitivity and specificity of quantitative ultrasound will be calculated against surgical pathologic response documented after surgery.	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 (Actual): June 13, 2018
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Ultrasound, Chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 308-2017

Drug and device information, study documents

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