Back to resultsA Pilot Study of Tomographic Optical Breast Imaging (DBT-TOBI) to Monitor Response to Neoadjuvant Therapy
Primary Purpose
Breast Cancer
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
DBT-TOBI
MRI-TOBI
Sponsored by
About this trial
This is an interventional diagnostic trial for Breast Cancer focused on measuring Breast Cancer, Optical imaging, neoadjuvant therapy
Eligibility Criteria
Inclusion Criteria:
- Female
- Participant will be receiving neoadjuvant chemotherapy at the Massachusetts General Hospital (MGH) Center for Breast Cancer.
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured as ≥10 mm in the longest diameter with breast MRI, mammography or ultrasound. See Section 11 for the evaluation of measurable disease.
- Patients must have Humane Epidermal Growth Factor Receptor (HER2) positive (regardless of Hormone Receptor (HR) status) or Triple Negative (TN) disease as confirmed by pathology. HER2 positive is defined according to ASCO-CAP guidelines, and patient will be receiving HER2 directed therapy. TN is defined as Estrogen Receptor <=1%, Progesterone Receptor <= 1%, and HER2 negative by American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines. For tumors with discordant or borderline receptor findings, the Principal Investigator will adjudicate the final decision.
- Age 18 and above.
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients with open wounds on the breast.
- Patients who have undergone breast surgery or breast biopsy 10 days or less prior to the first planned optical imaging scan.
- Patients with breast implants.
- Patients whose primary lesion is outside the field of view of the optical imaging system.
- A history of ipsilateral disease (including invasive breast cancer, ductal carcinoma in situ (DCIS), and benign lesions) or breast surgery.
- Patients who are pregnant or trying to become pregnant.
- Medical or psychiatric conditions which, in the opinion of the investigator, might result in risk to the subject from participation in the study or inability to complete the study.
For patients who agree to participate in the optional MRI study, these following additional exclusion criteria also apply:
- Neurostimulators;
- Pacemakers;
- Implanted metallic material or devices (metal implants or large tattoos in the field of view);
- Severe claustrophobia;
- Physical characteristics (weight and/or size) that exceed the capabilities of the MRI scanner;
- Known allergy or hypersensitivity reactions to gadolinium, versetamide, or any of the inert ingredients in gadolinium-based contrast agents;
- Severe renal insufficiency, e.g., estimated glomerular filtration rate < 30 mL/min.
Sites / Locations
- Massachusetts General Hospital Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DBT-TOBI
Arm Description
Subjects will be imaged using DBT-TOBI at the time points indicated in the Study Calendar (Baseline, before cycle 2, and additional optional time points). Both breasts will be measured in turn. Each breast is symmetrically centered on the x-ray detector/optical illuminator and is first compressed according to standard mammography procedures to determine the amount of force needed for each given patient An optional Magnetic Resonance Imaging TOBI (MRI-TOBI) scan will also be performed.
Outcomes
Primary Outcome Measures
Determining whether DBT-TOBI total hemoglobin concentration measurements before cycle 3 of chemotherapy can predict pathological complete response (pCR) versus non-complete responses in breast cancer.
The primary aim is to evaluate whether early measurements of the total hemoglobin concentration ratio in the primary tumor vs. the surrounding tissue, as estimated by our DBT-TOBI system, can predict neoadjuvant chemotherapy response at the time of surgery. Measurements will be obtained at baseline and just before cycle 3 to determine whether DBT-TOBI is predictive of pathological complete response (pCR) versus non-complete response for Human Epidermal Growth Factor Receptor 2 (HER2) positive and Triple negative breast cancer patients undergoing neoadjuvant chemotherapy.
Secondary Outcome Measures
Determining the predictive performance of early DBT-TOBI scans before the 3rd cycle of chemotherapy in distinguishing pCR versus non-pCR based on changes in tissue hemoglobin oxygen saturation.
DBT-TOBI measurements of the changes in the ratio of hemoglobin oxygen saturation in the primary tumor versus surrounding normal area between the pre-treatment baseline and immediately before the 3rd cycle of therapy will be used to predict pathological outcome at surgery. The outcome will be quantified using the area under the curve (AUC) after estimating an empirical receiver operating characteristic (ROC) curve for predicting pCR vs non-pCR.
Determining whether other optical parameters measured by DBT-TOBI are predictive of the final pathologic response after neoadjuvant therapy.
DBT-TOBI will be used to measure changes in the ratio of tumor to normal hemoglobin oxygen saturation ratio (SO2,T/N) between the baseline and prior to cycle 3 scans, as well as changes in the temporal response of total hemoglobin concentration (HbTT/N) or oxygen saturation (SO2,T/N) under constant mammographic compression.
Determining whether DBT-TOBI total hemoglobin concentration measurements before the cycle 2 and after changing chemotherapy can predict pathological complete response (pCR) versus non-complete responses in breast cancer.
DBT-TOBI measurements of the changes in the ratio of total hemoglobin concentration in the primary tumor versus surrounding normal area between the pre-treatment baseline and immediately before the 2nd cycle of therapy and immediately before any change in chemotherapy will be used to predict pathological outcome at surgery.
To investigate the ability of DBT-TOBI measurements to predict Residual Cancer Burden (RCB) groups 0 and 1 versus 2 and 3.
The various DBT-TOBI measurements (including the changes in the ratio of total hemoglobin concentration or oxygen saturation in the primary tumor versus surrounding normal area) between the pre-treatment baseline and immediately before the 3rd cycle of therapy and immediately before any change in chemotherapy will be used to predict pathological outcome at surgery. For this objective, the Residual Cancer Burden (RCB) categorization will be used and RCB 0/1 will be compared to RCB 2/3.
To investigate whether compression response-based optical property metrics are associated with lesion stiffness as measured by Magnetic Resonance Elastography.
The DBT-TOBI measurements under mammographic compression will be used to compare to the the measurements of tumor stiffness by Magnetic Resonance Imaging elastography. These measurements will be made at baseline and before the 3rd cycle of chemotherapy.
To assess the threshold values for detecting pathologic Complete Response (pCR) versus non-PCR and Residual Cancer Burden (RCB) 0/1 versus RCB 2/3, respectively, for changes in optical parameters at standard time points.
For this aim, a Receiver Operator Curve (ROC) will be estimated and used to determine the optimum cut-off value of optical parameters measured by DBT-TOBI from baseline to just prior to the 2nd or 3rd therapy cycle of chemotherapy, and from just before any chemotherapy change to just before the 2nd cycle with the second agent (as applicable), that distinguishes pCR from non-pCR and separately for RCB 0/1 from RCB 2/3.
To assess the threshold values for detecting pCR vs. non-PCR and RCB 0/1 versus RCB 2/3, respectively, for changes in MR derived tumor morphology from baseline to just prior the 3rd therapy cycle.
For this aim, a Receiver Operator Curve (ROC) will be estimated and used to determine the optimum cut-off value of MR derived tumor morphology from baseline to just prior to the 2nd or 3rd therapy cycle of chemotherapy, and from just before any chemotherapy change to just before the 2nd cycle with the second agent (as applicable), that distinguishes pCR from non-pCR and separately for RCB 0/1 from RCB 2/3.
To compare the predictive abilities between the Receiver Operator Curve (ROC) developed using DBT-TOBI and MR derived tumor morphology measurements to determine which measure more accurately predicts pathologic response.
For this aim, the Receiver Operator Curves (ROC) developed in Outcome 7 (using DBT-TOBI optical parameters) and 8 (using MR derived tumor morphology) will be compared and the difference will be used to determine which measure more accurately identifies patients with pCR vs non-PCR and patients with RCB 0/1 versus RCB 2/3.
Full Information
NCT ID
NCT03822312
First Posted
December 22, 2018
Last Updated
December 21, 2022
Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03822312
Brief Title
A Pilot Study of Tomographic Optical Breast Imaging (DBT-TOBI) to Monitor Response to Neoadjuvant Therapy
Official Title
A Pilot Study of Digital Breast Tomosynthesis Guided Near-infrared Tomographic Optical Breast Imaging (DBT-TOBI) in Monitoring Response of Breast Cancer to Neoadjuvant Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research study is evaluating whether the use of digital breast tomosynthesis and near-infrared tomographic optical breast imaging (DBT-TOBI) scans can predict the response of triple negative or HER2+ breast cancer to neoadjuvant chemotherapy.
The study radiologic scan involved in this study is digital breast tomosynthesis (also called 3 Dimensional mammogram) combined with near-infrared tomographic optical breast imaging, or DBT-TOBI.
Detailed Description
This research study is a Pilot Study, which is the first time investigators are examining this study device for this indication.
The FDA (the U.S. Food and Drug Administration) has not approved DBT-TOBI as a diagnostic scan for this disease.
The DBT-TOBI scan system is designed to deliver low power laser lights through a person's body tissue and collect data about the light that is transmitted through. In this study, the DBT-TOBI will be used to scan the breast. The data that can be collected through the scan is the total hemoglobin concentration and hemoglobin oxygen saturation. Hemoglobin is the protein found in red blood cells that is responsible for carrying oxygen to the various tissues in the body. These two data types are thought to provide insight into the response of the breast cancer to neoadjuvant chemotherapy treatment response. The researchers are looking to find if these scans will help show changes in the hemoglobin levels, thus showing how the cancer is reacting to treatment. The study is focused on 2 types of breast cancer called triple negative breast cancer and Human Epidermal Growth Factor Receptor 2 (HER2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Breast Cancer, Optical imaging, neoadjuvant therapy
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DBT-TOBI
Arm Type
Experimental
Arm Description
Subjects will be imaged using DBT-TOBI at the time points indicated in the Study Calendar (Baseline, before cycle 2, and additional optional time points).
Both breasts will be measured in turn.
Each breast is symmetrically centered on the x-ray detector/optical illuminator and is first compressed according to standard mammography procedures to determine the amount of force needed for each given patient
An optional Magnetic Resonance Imaging TOBI (MRI-TOBI) scan will also be performed.
Intervention Type
Device
Intervention Name(s)
DBT-TOBI
Intervention Description
The DBT-TOBI scan system is designed to deliver low power laser lights through a person's body tissue and collect data about the light that is transmitted through
Intervention Type
Device
Intervention Name(s)
MRI-TOBI
Intervention Description
The MRI-TOBI scan system is designed to deliver low power laser lights through a person's body tissue and collect data about the light that is transmitted through. The MRI scan is completed at the same time as the TOBI scan. Participation in this part of the intervention is optional.
Primary Outcome Measure Information:
Title
Determining whether DBT-TOBI total hemoglobin concentration measurements before cycle 3 of chemotherapy can predict pathological complete response (pCR) versus non-complete responses in breast cancer.
Description
The primary aim is to evaluate whether early measurements of the total hemoglobin concentration ratio in the primary tumor vs. the surrounding tissue, as estimated by our DBT-TOBI system, can predict neoadjuvant chemotherapy response at the time of surgery. Measurements will be obtained at baseline and just before cycle 3 to determine whether DBT-TOBI is predictive of pathological complete response (pCR) versus non-complete response for Human Epidermal Growth Factor Receptor 2 (HER2) positive and Triple negative breast cancer patients undergoing neoadjuvant chemotherapy.
Time Frame
4 to 6 months
Secondary Outcome Measure Information:
Title
Determining the predictive performance of early DBT-TOBI scans before the 3rd cycle of chemotherapy in distinguishing pCR versus non-pCR based on changes in tissue hemoglobin oxygen saturation.
Description
DBT-TOBI measurements of the changes in the ratio of hemoglobin oxygen saturation in the primary tumor versus surrounding normal area between the pre-treatment baseline and immediately before the 3rd cycle of therapy will be used to predict pathological outcome at surgery. The outcome will be quantified using the area under the curve (AUC) after estimating an empirical receiver operating characteristic (ROC) curve for predicting pCR vs non-pCR.
Time Frame
4-6 months
Title
Determining whether other optical parameters measured by DBT-TOBI are predictive of the final pathologic response after neoadjuvant therapy.
Description
DBT-TOBI will be used to measure changes in the ratio of tumor to normal hemoglobin oxygen saturation ratio (SO2,T/N) between the baseline and prior to cycle 3 scans, as well as changes in the temporal response of total hemoglobin concentration (HbTT/N) or oxygen saturation (SO2,T/N) under constant mammographic compression.
Time Frame
4-6 months
Title
Determining whether DBT-TOBI total hemoglobin concentration measurements before the cycle 2 and after changing chemotherapy can predict pathological complete response (pCR) versus non-complete responses in breast cancer.
Description
DBT-TOBI measurements of the changes in the ratio of total hemoglobin concentration in the primary tumor versus surrounding normal area between the pre-treatment baseline and immediately before the 2nd cycle of therapy and immediately before any change in chemotherapy will be used to predict pathological outcome at surgery.
Time Frame
4-6 months
Title
To investigate the ability of DBT-TOBI measurements to predict Residual Cancer Burden (RCB) groups 0 and 1 versus 2 and 3.
Description
The various DBT-TOBI measurements (including the changes in the ratio of total hemoglobin concentration or oxygen saturation in the primary tumor versus surrounding normal area) between the pre-treatment baseline and immediately before the 3rd cycle of therapy and immediately before any change in chemotherapy will be used to predict pathological outcome at surgery. For this objective, the Residual Cancer Burden (RCB) categorization will be used and RCB 0/1 will be compared to RCB 2/3.
Time Frame
4-6 months
Title
To investigate whether compression response-based optical property metrics are associated with lesion stiffness as measured by Magnetic Resonance Elastography.
Description
The DBT-TOBI measurements under mammographic compression will be used to compare to the the measurements of tumor stiffness by Magnetic Resonance Imaging elastography. These measurements will be made at baseline and before the 3rd cycle of chemotherapy.
Time Frame
4-6 months
Title
To assess the threshold values for detecting pathologic Complete Response (pCR) versus non-PCR and Residual Cancer Burden (RCB) 0/1 versus RCB 2/3, respectively, for changes in optical parameters at standard time points.
Description
For this aim, a Receiver Operator Curve (ROC) will be estimated and used to determine the optimum cut-off value of optical parameters measured by DBT-TOBI from baseline to just prior to the 2nd or 3rd therapy cycle of chemotherapy, and from just before any chemotherapy change to just before the 2nd cycle with the second agent (as applicable), that distinguishes pCR from non-pCR and separately for RCB 0/1 from RCB 2/3.
Time Frame
4-6 months
Title
To assess the threshold values for detecting pCR vs. non-PCR and RCB 0/1 versus RCB 2/3, respectively, for changes in MR derived tumor morphology from baseline to just prior the 3rd therapy cycle.
Description
For this aim, a Receiver Operator Curve (ROC) will be estimated and used to determine the optimum cut-off value of MR derived tumor morphology from baseline to just prior to the 2nd or 3rd therapy cycle of chemotherapy, and from just before any chemotherapy change to just before the 2nd cycle with the second agent (as applicable), that distinguishes pCR from non-pCR and separately for RCB 0/1 from RCB 2/3.
Time Frame
4-6 months
Title
To compare the predictive abilities between the Receiver Operator Curve (ROC) developed using DBT-TOBI and MR derived tumor morphology measurements to determine which measure more accurately predicts pathologic response.
Description
For this aim, the Receiver Operator Curves (ROC) developed in Outcome 7 (using DBT-TOBI optical parameters) and 8 (using MR derived tumor morphology) will be compared and the difference will be used to determine which measure more accurately identifies patients with pCR vs non-PCR and patients with RCB 0/1 versus RCB 2/3.
Time Frame
4-6 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female
Participant will be receiving neoadjuvant chemotherapy at the Massachusetts General Hospital (MGH) Center for Breast Cancer.
Participants must have measurable disease, defined as at least one lesion that can be accurately measured as ≥10 mm in the longest diameter with breast MRI, mammography or ultrasound. See Section 11 for the evaluation of measurable disease.
Patients must have Humane Epidermal Growth Factor Receptor (HER2) positive (regardless of Hormone Receptor (HR) status) or Triple Negative (TN) disease as confirmed by pathology. HER2 positive is defined according to ASCO-CAP guidelines, and patient will be receiving HER2 directed therapy. TN is defined as Estrogen Receptor <=1%, Progesterone Receptor <= 1%, and HER2 negative by American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines. For tumors with discordant or borderline receptor findings, the Principal Investigator will adjudicate the final decision.
Age 18 and above.
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Patients with open wounds on the breast.
Patients who have undergone breast surgery or breast biopsy 10 days or less prior to the first planned optical imaging scan.
Patients with breast implants.
Patients whose primary lesion is outside the field of view of the optical imaging system.
A history of ipsilateral disease (including invasive breast cancer, ductal carcinoma in situ (DCIS), and benign lesions) or breast surgery.
Patients who are pregnant or trying to become pregnant.
Medical or psychiatric conditions which, in the opinion of the investigator, might result in risk to the subject from participation in the study or inability to complete the study.
For patients who agree to participate in the optional MRI study, these following additional exclusion criteria also apply:
Neurostimulators;
Pacemakers;
Implanted metallic material or devices (metal implants or large tattoos in the field of view);
Severe claustrophobia;
Physical characteristics (weight and/or size) that exceed the capabilities of the MRI scanner;
Known allergy or hypersensitivity reactions to gadolinium, versetamide, or any of the inert ingredients in gadolinium-based contrast agents;
Severe renal insufficiency, e.g., estimated glomerular filtration rate < 30 mL/min.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Isakoff, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor- Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication.
IPD Sharing Access Criteria
Requests may be directed to: [contact information for Sponsor- Investigator or designee].
Learn more about this trial
A Pilot Study of Tomographic Optical Breast Imaging (DBT-TOBI) to Monitor Response to Neoadjuvant Therapy
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