TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Tumor permeability assessed by TMEM-MRI
研究概览
简要总结
The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer - Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI).
详细描述
The primary objective of this study is to develop a magnetic resonance imaging (MRI) based method for assessing TMEM-mediated permeability associated with cancer cell dissemination in breast cancer patients. TMEM-MRI has the ability to detect tumor areas with more leakiness (perfusion), where cancer cells 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
No need for masking, all patients will undergo TMEM-MRI
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •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. Glomerular Filtration Rate (GFR) should be greater than 30 mL/min/1.73 m
- •Weight less than or equal to the MRI table limit.
- •Ability to understand and willingness to sign a written informed consent.
排除标准
- •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.
研究组 & 干预措施
Pre-biopsy patients (Cohort A)
Patients identified by radiologist at the time of diagnostic evaluation and TMEM-MRI scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional fine-needle aspiration (FNA) preceding the core biopsy). 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 per National Comprehensive Cancer Network/American Society of Clinical Oncology (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).
干预措施: TMEM-MRI (Device)
Pre-biopsy patients (Cohort A)
Patients identified by radiologist at the time of diagnostic evaluation and TMEM-MRI scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional fine-needle aspiration (FNA) preceding the core biopsy). 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 per National Comprehensive Cancer Network/American Society of Clinical Oncology (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).
干预措施: FNA (Procedure)
Post-biopsy patients (Cohort B)
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.
干预措施: TMEM-MRI (Device)
Post-neoadjuvant therapy patients (Cohort C)
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 circulating tumor DNA (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.
干预措施: TMEM-MRI (Device)
结局指标
主要结局
Tumor permeability assessed by TMEM-MRI
时间窗: 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.
次要结局
- 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)
- TMEM density in breast cancer patients(Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes)
- MenaCalc(Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes)
- MenaInv(Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes)
- 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)