TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer

Montefiore Medicine Academic Health System

Status: Enrolling

Conditions: Breast Cancer

Treatments: Procedure: FNA; Device: TMEM-MRI

Study type: Interventional

Funder types: Other

Identifiers

NCT03694756

2018-9529

Details and patient eligibility

About

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).

Full description

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).

Enrollment: 95 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

• Eastern Cooperative Oncology Group (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. Glomerular Filtration Rate (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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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95 participants in 3 patient groups

Pre-biopsy patients (Cohort A)

Other group

Description:

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).

Treatment:

Device: TMEM-MRI

Procedure: FNA

Post-biopsy patients (Cohort B)

Other group

Description:

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.

Treatment:

Device: TMEM-MRI

Post-neoadjuvant therapy patients (Cohort C)

Other group

Description:

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.

Treatment:

Device: TMEM-MRI