Pilot Investigation of Ultrasound Imaging and Spectroscopy and Ultrasound Imaging of Vascular Blood Flow as Early Indicators of Locally-Advanced Breast Cancer Response to Neoadjuvant Treatment

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Sunnybrook Health Sciences Centre.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Dr. Gregory Czarnota, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT00437879
First received: February 20, 2007
Last updated: April 25, 2012
Last verified: April 2012
  Purpose

We 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. The objectives of this study are to evaluate the use of ultrasound imaging and spectroscopy as a predictive marker of advanced tumour response to combined chemotherapy and radiotherapy. Since neoadjuvant treatments may also act on tumour vasculature to "normalize" it we will also evaluate blood-vessel imaging by standard Doppler-imaging and with standard higher-resolution imaging using clinically approved microbubble contrast agents.

The main goal, as described above, is to select the best ultrasound spectroscopy parameter to use as an early predictor of pathological complete response.


Condition
Locally Advanced Breast Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Pilot Investigation of Ultrasound Imaging and Spectroscopy and Ultrasound Imaging of Vascular Blood Flow as Early Indicators of Locally-Advanced Breast Cancer Response to Neoadjuvant Treatment

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Estimated Enrollment: 100
Study Start Date: January 2007
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Detailed Description:

We 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. The objectives of this study are to evaluate the use of ultrasound imaging and spectroscopy as a predictive marker of advanced tumour response to combined chemotherapy and radiotherapy. Since neoadjuvant treatments may also act on tumour vasculature to "normalize" it we will also evaluate blood-vessel imaging by standard Doppler-imaging and with standard higher-resolution imaging using clinically approved microbubble contrast agents.

The main goal, as described above, is to select the best ultrasound spectroscopy parameter to use as an early predictor of pathological complete response.

Specifically, we will as a primary endpoint correlate changes in ultrasound backscatter parameters obtained throughout the course of treatment with pathological complete, partial, or complete and partial response. We ultimately hope to be able to generate a Receiver-Operator-Curve for each parameter beyond this pilot investigation. The ultrasound-spectroscopy parameters to be examined include mid-band fit, spectral-slope and histogram-distribution-fit parameters related to scatterer size and concentration. From these various receiver-operator curves the best ultrasound parameter for predicting response will be selected and will aid to define the clinical specificity and sensitivity of the technique.

The secondary endpoint in this study will include examining the change in size of the tumour, which will also be measured using conventional gold-standard B-scan ultrasound imaging (length by width by height in addition to volume) and correlating that to the spectroscopic ultrasound changes determined at different times during patient treatment.

Other secondary endpoints will include measuring changes in blood vessel distribution by standard Doppler-imaging and standard microbubble contrast agent imaging. As another secondary endpoint we will also correlate our ultrasound changes with 2 and 5-year long-term clinical outcome.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Women who are receiving neoadjuvant chemotherapy or neoadjuvant chemo-radiotherapy for locally-advanced breast cancer.

Criteria

Inclusion Criteria:

The following criteria are necessary for study participation:

  1. Histologically or cytologically confirmed locally advanced breast carcinoma which has not been treated with any first-line therapy and will be treated with neoadjuvant chemotherapy or neoadjuvant combined chemo-radiotherapy
  2. Measurable disease 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:

    • hemoglobin >90 mg/dL
    • leukocytes >3,000/mL
    • absolute neutrophil count >1,500/mL
    • platelets >100,000/mL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
    • 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:

The following conditions will exclude women from participation:

  1. Chemotherapy, radiotherapy, or major surgery within 4 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:

    • previous radiotherapy to an involved area
    • active collagen vascular disease
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00437879

Contacts
Contact: Gregory J. Czarnota, Ph.D. M.D. 416-480-5329 Gregory.Czarnota@sunnybrook.ca
Contact: Jacqueline Spayne, Ph.D. M.D. 416-480-6100 Jacqueline.Spayne@sunnybrook.ca

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
Principal Investigator: Gregory J. Czarnota, Ph.D. M.D. Sunnybrook Health Sciences Centre
  More Information

No publications provided

Responsible Party: Dr. Gregory Czarnota, Dr., Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT00437879     History of Changes
Other Study ID Numbers: 185-2006
Study First Received: February 20, 2007
Last Updated: April 25, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by Sunnybrook Health Sciences Centre:
Breast Cancer
Ultrasound

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 18, 2014