DCE-MRI and MBI in Assessing Tumor Response to Chemotherapy in Patients With Triple Negative Breast Cancer

Multimodality Breast Imaging for the Assessment of Tumor Response to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients

This early phase I trial studies how well dynamic contrast enhanced molecular resonance imaging (DCE-MRI) and technetium-Tc99m sestamibi molecular breast imaging (MBI) work in assessing tumor response to chemotherapy in patients with triple negative breast cancer (TNBC) who are undergoing chemotherapy. Investigational imaging scans such as MBI and DCE-MRI may help researchers predict which patients may respond to treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Triple-Negative Breast Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Radiation: Scintimammography; Drug: Technetium Tc-99m Sestamibi

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the predictive value of advanced imaging modalities Tc99m sestamibi (technetium Tc-99m sestamibi) molecular breast imaging (MBI) and dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) for neoadjuvant chemotherapy (NAC) response in triple negative breast cancer (TNBC).

SECONDARY OBJECTIVES:

I. To evaluate and compare the ability all imaging modalities including standard of care digital mammogram (DM) and ultrasound (US) as well as novel modalities DCE-MRI and MBI to assess and predict response to neoadjuvant chemotherapy (NAC) in patients with triple negative breast cancer (TNBC).

EXPLORATORY OBJECTIVES:

I. To determine effect of molecular subtype of TNBC on diagnostic performance of different types of imaging modalities in predicting treatment response.

II. To determine the Utility of Dynamic Tc99m sestamibi MBI and DCE-MRI together with molecular profiling to identify a subgroup of chemoresistant TNBC patients.

OUTLINE:

Patients undergo DCE-MRI over 45-60 minutes. Patients receive technetium Tc-99m sestamibi via injection, and after 5 minutes patients undergo MBI scan over 1 hour. Both DCE-MRI and MBI are performed at the time of enrollment, at the end of anthracycline therapy, and at the conclusion of NAC before surgery. All patients also undergo standard of care imaging with DM and US (at the same time points if the treating doctor chooses to do so).

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77094
      • MD Anderson in Katy
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
    • Nassau Bay, Texas, United States, 77058
      • MD Anderson League City
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land
    • The Woodlands, Texas, United States, 77384
      • MD Anderson in The Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient has proven TNBC, defined by standard pathologic assays as negative for estrogen receptor (ER) and progesterone receptor (PR) (< 10% tumor staining) and negative for human epidermal growth factor 2 (HER2) (immunohistochemistry [IHC] score < 3, gene copy number not amplified)
• TNBC patients who are previously untreated and enrolled in the prospective Institutional Review Board (IRB) approved clinical trial: 2014-0185
• Patients who are able to understand and give consent to participating in the study

Exclusion Criteria:

• Is pregnant (confirmed by the patient as imaging clinic standard of care) or nursing mother
• Has lesions involving chest wall
• Has known allergy to Tc99m sestamibi
• Has known contraindications to MRI
• Has contraindication to MRI contrast

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (DCE-MRI, MBI); Patients undergo DCE-MRI over 45-60 minutes. Patients receive technetium Tc-99m sestamibi via injection, and after 5 minutes patients undergo MBI scan over 1 hour. Both DCE-MRI and MBI are performed at the time of enrollment, at the end of anthracycline therapy, and at the conclusion of NAC before surgery. All patients also undergo standard of care imaging with DM and US (at the same time points if the treating doctor chooses to do so).

Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE-MRI; Other Names: DCE-MRI; DCE MRI; DYNAMIC CONTRAST ENHANCED MRI; Radiation: Scintimammography; Undergo MBI; Other Names: MBI; Breast-Specific Gamma Imaging; Miraluma Scan; Miraluma Test; Molecular Breast Imaging; Nuclear Medicine Breast Imaging; sestamibi breast imaging; Sestamibi Scintimammography; Drug: Technetium Tc-99m Sestamibi; Given via injection; Other Names: Cardiolite; Miraluma; Tc 99m Sestamibi; Tc-99m MIBI; Tc99m Sestamibi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in volume of index tumors and estimated area under receiver operating characteristic (ROC) curves assessed by digital mammogram, ultrasound, dynamic contrast enhanced molecular resonance imaging (DCE-MRI) and molecular breast imaging (MBI)	The ability to assess and predict response will be compared among the imaging modalities and with standard pathological evaluation. These volume changes will be correlated with residual cancer burden (RCB) status after surgery and will be used to classify patients into predicted responder or non-responder categories. Predictive accuracies among the imaging modalities will be compared using paired ROC curve analyses.	Up to 4 years
Percent change in tumor volume assessed by dynamic Tc99m-sestamibi MBI	The index tumor will be measured on both cranial-caudal (CC) and medio-lateral oblique (MLO) views and 3 dimension will be recorded. The percentage change in volume at time points 2 and 3 relative to baseline imaging (time point 1) will be calculated. Data acquisition and image processing algorithms will be developed from having conjugate views of the breast in the MBI examination. Appropriate methods to correct the image from loss of contrast due to scatter and loss of signal from photon attenuation as it transits breast tissue will be explored and implemented. Will investigate the correlations of absolute and relative values of baseline standardized uptake value (SUVb) with pathological tumor response.	up to 6 months
Tumor response assessed by pathological examination	Correlations of pathological response with absolute and relative values of MBI SUVb will be investigated. The longest dimension of the residual tumor will be measured. If only foci of disease are seen the longest dimension of tumor cell distribution will be measured. The M D Anderson Cancer Center (MDACC) Residual Cancer Burden Calculator will be used to categorize cancer burden: RCB-0 (no residual disease in breast or in lymph nodes), RCB-1 (minimal residual disease), RCB-2 (moderate residual disease), or RCB-3 (extensive residual disease).	Up to 4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility of molecular breast imaging (MBI) and dynamic contrast enhanced molecular resonance imaging (DCE-MRI) together with molecular profiling to identify a subgroup of chemoresistant triple negative breast cancer (TNBC) patients	Assessed by baseline SUVb and baseline genomic signature. Will fit one logistic regression model with baseline SUVb and baseline genomic signature as covariates and response to the upfront chemotherapy as the endpoint and one model with baseline DCE-MRI tumor volume and baseline genomic signature as covariates and response to the upfront chemotherapy as the endpoint. Will assess the predictive accuracy of this model by estimating the area under the ROC curve using the predicting response probability and the observed response outcome. ROC curves will be generated for each modality and each TNBC molecular subtype and compute the areas under these curves along with 95% confidence intervals. Will determine a cut-point in the predicted probabilities to classify patients as predicted responders and non-responders based an appropriate trade-off between sensitivity and specificity.	up to 6 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gaiane M Rauch, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2016
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimated): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Technetium Tc 99m Sestamibi
• Other Study ID Numbers: 2015-0816 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2016-00715 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No