Locally Advanced Breast Cancer Clinical Trial in Toronto Ontario
NCT00437879
| Observational
This study is looking to recruit 600 Participants
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.
Details for the study
Population
Women who are receiving neoadjuvant chemotherapy or neoadjuvant chemo-radiotherapy for
locally-advanced breast cancer.
Brief 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
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
Brief Summary
We have previously demonstrated that high-frequency ultrasound and spectroscopy, and recently<br /> conventional-frequency ultrasound and spectroscopy may be used to detect cell death in vitro,<br /> in situ and in vivo. The method can detect different forms of cell death and has been<br /> demonstrated to be sensitive to apoptotic, necrotic and mitotic cell death. The objectives of<br /> this study are to evaluate the use of ultrasound imaging and spectroscopy as a predictive<br /> marker of advanced tumour response to combined chemotherapy and radiotherapy. Since<br /> neoadjuvant treatments may also act on tumour vasculature to "normalize" it we will also<br /> evaluate blood-vessel imaging by standard Doppler-imaging and with standard higher-resolution<br /> imaging using clinically approved microbubble contrast agents.<br /><br /> The main goal, as described above, is to select the best ultrasound spectroscopy parameter to<br /> use as an early predictor of pathological complete response.
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 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.