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

Sponsor
Sunnybrook Health Sciences Centre (Other)
Overall Status
Recruiting
CT.gov ID
NCT00437879
Collaborator
(none)
600
1
269
2.2

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase

    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.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    600 participants
    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
    Study Start Date :
    Jan 1, 2007
    Anticipated Primary Completion Date :
    Jun 1, 2027
    Anticipated Study Completion Date :
    Jun 1, 2029

    Outcome Measures

    Primary Outcome Measures

      Eligibility Criteria

      Criteria

      Ages Eligible for Study:
      N/A and Older
      Sexes Eligible for Study:
      Female
      Accepts Healthy Volunteers:
      No
      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

      1. 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

      1. Any clinically serious infections requiring systemic anti-bacterial, antifungal or antiviral therapy

      2. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia

      3. Psychiatric illness/social situations that would limit compliance with study requirements

      4. History of active ongoing seizure disorder

      5. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

      6. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

      Contacts and Locations

      Locations

      Site City State Country Postal Code
      1 Sunnybrook Health Sciences Centre 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

      Study Documents (Full-Text)

      None provided.

      More Information

      Publications

      None provided.
      Responsible Party:
      Dr. Gregory Czarnota, Dr., Sunnybrook Health Sciences Centre
      ClinicalTrials.gov Identifier:
      NCT00437879
      Other Study ID Numbers:
      • 185-2006
      First Posted:
      Feb 21, 2007
      Last Update Posted:
      Aug 3, 2022
      Last Verified:
      Aug 1, 2022
      Keywords provided by Dr. Gregory Czarnota, Dr., Sunnybrook Health Sciences Centre
      Additional relevant MeSH terms:

      Study Results

      No Results Posted as of Aug 3, 2022