TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Device: TMEM-MRIProcedure: FNA
- Registration Number
- NCT03694756
- Lead Sponsor
- Montefiore Medical Center
- Brief Summary
The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer (TMEM-MRI)
- Detailed Description
The goal of this study is to assess the feasibility of a new imaging technology in the management of breast cancer. Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI) has the ability to detect tumor areas with more leakiness (perfusion), where cancer cell enter blood vessels to travel to other sites. This novel TMEM-MRI has potential to be used in clinical practice to identify tumors with high leakiness that might have higher chances to recur after breast cancer treatment. In addition, TMEM-MRI can potentially be used to assess response to preoperative treatments (chemotherapy, hormonal therapy) over time.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pre-biopsy patients (Cohort A) TMEM-MRI Patients identified by a radiologist at the time of diagnostic evaluation. Upon consent, TMEM-MRI will be scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional FNA preceding the core biopsy). MenaINV and MenaCalc will be calculated from the FNA material. After the breast biopsy confirms the suspected diagnosis of invasive breast carcinoma, the patient will be referred to breast surgery and a treatment plan devised, as per NCCN/ASCO guidelines. No patients were enrolled into this arm/group and Cohort A has been removed by protocol amendment. This was intended to be a cohort for patients before breast biopsy in the event the biopsy procedure created a hematoma which would, in turn, affect measurement of TMEM-MRI activity. Since this effect was not observed in the first set of patients enrolled, Cohort A was removed from the study and only patients post-breast biopsy were enrolled (Cohort B). Pre-biopsy patients (Cohort A) FNA Patients identified by a radiologist at the time of diagnostic evaluation. Upon consent, TMEM-MRI will be scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional FNA preceding the core biopsy). MenaINV and MenaCalc will be calculated from the FNA material. After the breast biopsy confirms the suspected diagnosis of invasive breast carcinoma, the patient will be referred to breast surgery and a treatment plan devised, as per NCCN/ASCO guidelines. No patients were enrolled into this arm/group and Cohort A has been removed by protocol amendment. This was intended to be a cohort for patients before breast biopsy in the event the biopsy procedure created a hematoma which would, in turn, affect measurement of TMEM-MRI activity. Since this effect was not observed in the first set of patients enrolled, Cohort A was removed from the study and only patients post-breast biopsy were enrolled (Cohort B). Post-biopsy patients (Cohort B) TMEM-MRI Patients after breast biopsy. Once consent is obtained, patients will undergo TMEM-MRI. The patients will undergo definitive breast surgery and will receive adjuvant treatments as per NCCN/ASCO guidelines. TMEM density, MenaCalc and MenaINV will be evaluated in final surgical specimen. Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV. Post-neoadjuvant therapy patients (Cohort C) TMEM-MRI Patients status post neoadjuvant therapy. Patients who received neoadjuvant will be enrolled into Cohort C to understand the correlation between TMEM MRI activity and TMEM doorway density following after neoadjuvant chemotherapy. Only patients with residual palpable mass on physical exam will be included (≥ 1cm). Patients will undergo TMEM-MRI after neoadjuvant therapy is completed. Patients will also have CTCs and ctDNA measured on the same day of TMEM-MRI (+/- 3 days). TMEM density, MenaCalc and MenaINV will be evaluated in breast surgical specimen (after pre-operative therapy). Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV after pre-operative therapy.
- Primary Outcome Measures
Name Time Method Tumor permeability assessed by TMEM-MRI Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery Tumor permeability will be assessed by TMEM-MRI, and is defined as a number of Uth units (the number of tumor voxels with permeability density above threshold divided by the number of all tumor voxels) that will be obtained from the permeability map and TMEM-MRI algorithm.
- Secondary Outcome Measures
Name Time Method TMEM density in breast cancer patients Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from FFPE breast cancer specimen resected for therapeutic purposes TMEM density is defined as the number of TMEM units visualized by triple immunohistochemistry in 10 high power fields (40X). TMEM density will be measured with a fully automated and scalable clinical assay for identification and enumeration of TMEM utilizing digital pathology methods coupled with image analysis
MenaCalc Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from FFPE breast cancer specimen resected for therapeutic purposes MenaCalc is calculated by subtracting the Z-score value of Mena11a from the Z-score value of pan-Mena, obtained by quantitative immunohistochemistry in formalin-fixed paraffin-embedded breast tumor specimens. MenaCalc can also be measured by qRT-PCR in cancer cells obtained by FNA
MenaInv Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from FFPE breast cancer specimen resected for therapeutic purposes MenaInv is calculated as pixel intensity obtained by quantitative immunofluorescence per area of formalin-fixed paraffin-embedded tumor tissue. MenaINV can also be measured by qRT-PCR in cancer cells obtained by FNA
Circulating Tumor Cells (CTCs) Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery CTCs will detected and enumerated from peripheral blood samples using EPIC sciences or RareCyte platform. Patients will undergo venipuncture to obtain specimen for CTC assays. Specimens will be shipped to EPIC sciences (using CTC liquid biopsy blood collection kit) or the University of Southern California (using RareCyte collection kit) to be processed and analyzed as per respective protocols. CTCs will be measured +/- 3 days of TMEM-MRI. Group mean results in number of cells/mL of peripheral blood will be reported for patients in pilot phase Cohort B and pilot phase Cohort C.
Trial Locations
- Locations (1)
Montefiore Medical Center
🇺🇸Bronx, New York, United States