Brief Summary
The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer (TMEM-MRI)
Brief Title
TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer
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.
In a prior study, it was found that patients with high TMEM doorway score, compared to patients with mid/low TMEM doorway score, in their residual disease after neoadjuvant therapy, had worse distant relapse-free survival (p = 0.008). These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development of the proposed TMEM MRI in humans, the tumor microenvironment is naïve to treatment. However, neoadjuvant therapy may affect the tumor microenvironment which could affect vascular anatomy - a key component of the TMEM MRI algorithm. Therefore, the study team aims to assess the correlation between TMEM doorway density and TMEM MRI activity after neoadjuvant therapy (Pilot Cohort C).
In a prior study, it was found that patients with high TMEM doorway score, compared to patients with mid/low TMEM doorway score, in their residual disease after neoadjuvant therapy, had worse distant relapse-free survival (p = 0.008). These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development of the proposed TMEM MRI in humans, the tumor microenvironment is naïve to treatment. However, neoadjuvant therapy may affect the tumor microenvironment which could affect vascular anatomy - a key component of the TMEM MRI algorithm. Therefore, the study team aims to assess the correlation between TMEM doorway density and TMEM MRI activity after neoadjuvant therapy (Pilot Cohort C).
Central Contacts
Central Contact Role
Contact
Central Contact Phone
7184058505
Central Contact Email
janampa@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Breast Cancer
Eligibility Criteria
Inclusion Criteria
* For pre-pilot phase (MRI sequence development):
o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)
* For pilot phase Cohort A:
o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).
* For pilot phase Cohort B:
* Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
* No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
* For pilot phase Cohort C:
* Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
* Residual palpable mass \> 1 cm in largest diameter after neoadjuvant therapy.
* Candidate for breast MRI before definitive surgery.
* Tumor size/breast mass should be \> 1 cm in largest diameter (radiologically).
* Multifocal disease is allowed, as long as patients meet all eligibility criteria.
* Age ≥ 18 years.
* ECOG performance status 0-1.
* Willingness to undergo a "research breast MRI".
* Patient must be able to undergo MRI with gadolinium enhancement.
* No history of untreatable claustrophobia.
* No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
* No history of sickle cell disease.
* No contraindication to intravenous contrast administration.
* No known allergy-like reaction to gadolinium
* No known or suspected renal impairment. GFR should be greater than 30 mL/min/1.73 m2.
* Weight less than or equal to the MRI table limit.
* Ability to understand and willingness to sign a written informed consent.
Exclusion Criteria
* Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
* No breast prosthetic implants (silicone or saline) are allowed.
* Use of any investigational agent within 30 days of starting study.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
* Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.
* For pre-pilot phase (MRI sequence development):
o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)
* For pilot phase Cohort A:
o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).
* For pilot phase Cohort B:
* Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
* No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
* For pilot phase Cohort C:
* Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
* Residual palpable mass \> 1 cm in largest diameter after neoadjuvant therapy.
* Candidate for breast MRI before definitive surgery.
* Tumor size/breast mass should be \> 1 cm in largest diameter (radiologically).
* Multifocal disease is allowed, as long as patients meet all eligibility criteria.
* Age ≥ 18 years.
* ECOG performance status 0-1.
* Willingness to undergo a "research breast MRI".
* Patient must be able to undergo MRI with gadolinium enhancement.
* No history of untreatable claustrophobia.
* No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
* No history of sickle cell disease.
* No contraindication to intravenous contrast administration.
* No known allergy-like reaction to gadolinium
* No known or suspected renal impairment. GFR should be greater than 30 mL/min/1.73 m2.
* Weight less than or equal to the MRI table limit.
* Ability to understand and willingness to sign a written informed consent.
Exclusion Criteria
* Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
* No breast prosthetic implants (silicone or saline) are allowed.
* Use of any investigational agent within 30 days of starting study.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
* Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.
Inclusion Criteria
Inclusion Criteria
* For pre-pilot phase (MRI sequence development):
o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)
* For pilot phase Cohort A:
o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).
* For pilot phase Cohort B:
* Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
* No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
* For pilot phase Cohort C:
* Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
* Residual palpable mass \> 1 cm in largest diameter after neoadjuvant therapy.
* Candidate for breast MRI before definitive surgery.
* Tumor size/breast mass should be \> 1 cm in largest diameter (radiologically).
* Multifocal disease is allowed, as long as patients meet all eligibility criteria.
* Age ≥ 18 years.
* ECOG performance status 0-1.
* Willingness to undergo a "research breast MRI".
* Patient must be able to undergo MRI with gadolinium enhancement.
* No history of untreatable claustrophobia.
* No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
* No history of sickle cell disease.
* No contraindication to intravenous contrast administration.
* No known allergy-like reaction to gadolinium
* No known or suspected renal impairment. GFR should be greater than 30 mL/min/1.73 m2.
* Weight less than or equal to the MRI table limit.
* Ability to understand and willingness to sign a written informed consent.
* For pre-pilot phase (MRI sequence development):
o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)
* For pilot phase Cohort A:
o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).
* For pilot phase Cohort B:
* Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
* No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
* For pilot phase Cohort C:
* Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
* Residual palpable mass \> 1 cm in largest diameter after neoadjuvant therapy.
* Candidate for breast MRI before definitive surgery.
* Tumor size/breast mass should be \> 1 cm in largest diameter (radiologically).
* Multifocal disease is allowed, as long as patients meet all eligibility criteria.
* Age ≥ 18 years.
* ECOG performance status 0-1.
* Willingness to undergo a "research breast MRI".
* Patient must be able to undergo MRI with gadolinium enhancement.
* No history of untreatable claustrophobia.
* No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
* No history of sickle cell disease.
* No contraindication to intravenous contrast administration.
* No known allergy-like reaction to gadolinium
* No known or suspected renal impairment. GFR should be greater than 30 mL/min/1.73 m2.
* Weight less than or equal to the MRI table limit.
* Ability to understand and willingness to sign a written informed consent.
Gender
All
Gender Based
false
Keywords
TMEM;
Magnetic resonance imaging (MRI);
breast cancer.
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03694756
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2018-9529
Overall Status
Recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer
Primary Outcomes
Outcome Description
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.
Outcome Measure
Tumor permeability assessed by TMEM-MRI
Outcome Time Frame
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
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
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
Outcome Measure
TMEM density in breast cancer patients
Outcome Description
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
Outcome Time Frame
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
Outcome Measure
MenaCalc
Outcome Description
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
Outcome Time Frame
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
Outcome Measure
MenaInv
Outcome Description
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.
Outcome Time Frame
Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery
Outcome Measure
Circulating Tumor Cells (CTCs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jesus Anampa Mesias
Investigator Email
janampa@montefiore.org
Investigator Phone
718-920-4826/718-405-8505/646-757-0997