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

NCT ID: NCT04050228

Last Updated: 2023-12-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-13
• Study Completion Date: 2029-06-30

Brief Summary

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.

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.

Conditions

Breast Cancer

Keywords

Ultrasound, Chemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Quantitative ultrasound to guide adaptive chemotherapy

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Gregory Czarnota

Radiation Oncologist and Clinician Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gregory J Czarnota, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Gregory J Czarnota, PhD, MD

Role: CONTACT

Phone: (416) 480-6128

Email: gregory.czarnota@sunnybrook.ca

Facility Contacts

Gregory J Czarnota, PhD, MD

Role: primary

References

Dasgupta A, DiCenzo D, Sannachi L, Gandhi S, Pezo RC, Eisen A, Warner E, Wright FC, Look-Hong N, Sadeghi-Naini A, Curpen B, Kolios MC, Trudeau M, Czarnota GJ. Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study. Front Oncol. 2024 Apr 19;14:1273437. doi: 10.3389/fonc.2024.1273437. eCollection 2024.

Reference Type: DERIVED

PMID: 38706611 (View on PubMed)

Other Identifiers

308-2017

Identifier Type: -

Identifier Source: org_study_id