Clinical trial NCT03694756: TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: TMEM;
Magnetic resonance imaging (MRI);
breast cancer.
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2018-10-03
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were originally intended to be enrolled in 2 cohorts (A and B), based on breast biopsy status; however, the study design was changed following Protocol Amendment.
Primary purpose: OTHER

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.

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).

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.

Primary outcomes:
measure: Tumor permeability assessed by TMEM-MRI
timeFrame: 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:
measure: TMEM density in breast cancer patients
timeFrame: 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
measure: MenaCalc
timeFrame: 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
measure: MenaInv
timeFrame: 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
measure: Circulating Tumor Cells (CTCs)
timeFrame: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Jesus Anampa, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: