TMEM-MRI Imaging for Breast Cancer

(TMEM-MRI Trial)

Overseen by Jesus Anampa, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Montefiore Medical Center

Must not be taking: Investigational agents

Disqualifiers: Breast cancer history, Implants, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer (TMEM-MRI)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have started any preoperative therapy for breast cancer before the TMEM-MRI is conducted.

What data supports the effectiveness of the TMEM-MRI treatment for breast cancer?

Research shows that TMEM-MRI can detect specific sites in tumors that are linked to the spread of cancer cells, and it correlates with the number of these sites in breast cancer patients. This imaging method can help assess the risk of cancer spreading and monitor how well treatments that block these sites are working. ^{1 2 3 4 5}

Is TMEM-MRI imaging safe for humans?

The research does not provide specific safety data for TMEM-MRI imaging in humans, but it suggests that the technique is used as a non-invasive test in breast cancer patients and mouse models, indicating it may be generally safe. ^{1 5 6 7 8}

How is TMEM-MRI treatment different from other breast cancer treatments?

TMEM-MRI is unique because it uses a special type of MRI to detect 'TMEM doorways' in the tumor, which are linked to the spread of cancer cells. This non-invasive imaging method helps assess the risk of metastasis and monitor the effectiveness of treatments that target these doorways, unlike traditional treatments that focus on directly attacking the tumor. ^{1 2 9 10 11}

Research Team

Jesus Anampa, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for adults over 18 with a breast mass larger than 1 cm, diagnosed as invasive breast carcinoma or highly suspicious of it. It's for those who haven't had preoperative therapy and can undergo an MRI with contrast, without any history of severe claustrophobia, metallic implants incompatible with MRI, sickle cell disease, known allergies to gadolinium, or renal impairment.

Inclusion Criteria

I have a breast mass confirmed as invasive breast cancer by biopsy.

My breast mass is highly likely to be cancer, as per my radiologist.

Criterion: For a specific part of the trial, participants must have a breast mass that is confirmed to be invasive ductal carcinoma through a core biopsy. The tumor should be able to be removed by surgery, and no treatment before surgery is planned. The tumor should be at least 1 cm in size. Participants must be at least 18 years old, have good performance status, be willing to undergo a research breast MRI with contrast, and meet certain medical requirements, such as having no metal objects in the body and no history of certain medical conditions.

Exclusion Criteria

Use of any investigational agent within 30 days of starting study

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I have never had breast cancer or radiation to the same breast before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

TMEM-MRI Imaging

Participants undergo TMEM-MRI to assess tumor permeability and TMEM density

2 weeks

1 visit (in-person)

Post-Imaging Analysis

Analysis of TMEM density, MenaCalc, and MenaINV from surgical specimens

0-56 days before surgery

Follow-up

Participants are monitored for safety and effectiveness after imaging and surgery

4 weeks

Treatment Details

Interventions

• FNA (Procedure)
• TMEM-MRI (Imaging Technology)

Trial Overview The study is testing the feasibility of TMEM-MRI technology in managing operable breast cancer. Participants will undergo a 'research breast MRI' using this new imaging technique alongside standard care to see how well it works in detecting and assessing their cancer.

Participant Groups

Group I: Pre-biopsy patients (Cohort A) Experimental Treatment 2 Interventions

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).

Group II: Post-neoadjuvant therapy patients (Cohort C) Experimental Treatment 1 Intervention

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.

Group III: Post-biopsy patients (Cohort B) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Andrew D. Racine

Montefiore Medical Center

Chief Medical Officer since 1992

MD, PhD from New York University; Undergraduate degree from Harvard University

Philip O. Ozuah

Montefiore Medical Center

Chief Executive Officer since 2019

MD, PhD from New York University

Findings from Research

TMEM Activity-MRI is a new imaging technique that can detect specific vascular openings associated with tumor microenvironment of metastasis (TMEM) in breast cancer, which are linked to the risk of cancer spreading.

This imaging method not only correlates with the number of TMEM doorways in tumors but also shows changes in response to treatments, such as decreased activity with the TMEM inhibitor rebastinib and increased activity with chemotherapy like paclitaxel, indicating its potential as a tool for assessing metastatic risk and monitoring treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy. Karagiannis, GS., Bianchi, A., Sanchez, LR., et al.[2023]

Functional MRI techniques, including dynamic contrast-enhanced MRI, are valuable for noninvasively assessing the blood flow and oxygenation of breast tumors, which can help predict how well they respond to neoadjuvant chemotherapy.

Advanced MRI methods like diffusion-weighted MRI and MR spectroscopy may provide insights into tumor cellularity and metabolism, enhancing our understanding of breast carcinoma characteristics during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging and blood oxygenation level-dependent magnetic resonance imaging for the assessment of changes in tumor biology with treatment. Li, SP., Padhani, AR., Makris, A.[2015]

Advanced MRI techniques can provide crucial functional and structural information about tumors, such as oxygen levels, cellular growth, and blood flow, which are essential for understanding the tumor microenvironment.

Integrating these diverse MRI methods can significantly enhance tumor detection, characterization, and treatment monitoring in cancer patients, leading to better risk assessment and drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of magnetic resonance imaging in oncology. González Hernando, C., Esteban, L., Cañas, T., et al.[2021]

Preclinical imaging strategies have revealed three distinct types of brain metastases from breast cancer: permeable metastases, nonpermeable metastases, and solitary dormant cancer cells, each likely requiring different therapeutic approaches.

Current MRI techniques may not fully capture the extent of metastatic disease in the brain, suggesting that a better understanding of these metastases could lead to the development of more effective treatments that can cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. Murrell, DH., Foster, PJ., Chambers, AF.[2021]

The study used dynamic contrast-enhanced MRI to analyze tumor blood flow and permeability in MCF7 human breast cancer implanted in mice, revealing that areas of rapid enhancement corresponded to regions with dense, permeable microcapillaries, particularly around necrotic areas.

The findings suggest that the degree of angiogenic activity induced by stress conditions in tumors, which was heightened in response to tamoxifen treatment, could provide valuable diagnostic and prognostic information when assessed through contrast-enhanced MRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors. Furman-Haran, E., Margalit, R., Grobgeld, D., et al.[2019]

The tumor microenvironment (TME) plays a crucial role in the progression and metastasis of cancers, including breast cancer, by influencing drug activity and efficacy.

Targeting specific components of the TME presents a novel therapeutic approach for treating breast cancer, highlighting the potential for new treatment strategies that go beyond traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress. Bahrami, A., Hassanian, SM., Khazaei, M., et al.[2018]

The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment resistance, with factors like tissue hypoxia and acidosis influencing cancer cell survival and normal cell toxicity.

Targeting and normalizing the redox parameters within the TME could potentially reduce the selection of aggressive cancer cell phenotypes, offering a new strategy for anticancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus-faced tumor microenvironment and redox. Khramtsov, VV., Gillies, RJ.[2021]

The study identifies Tumor MicroEnvironment of Metastasis (TMEM) doorways as critical sites for cancer cell dissemination in breast cancer, with their number being a prognostic indicator for metastatic recurrence.

Two methods for assessing TMEM-mediated vascular permeability—intravital imaging and fixed tissue immunofluorescence—are proposed, suggesting that combining these techniques can enhance understanding of how cancer cells spread and aid in developing treatments to prevent metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis. Karagiannis, GS., Pastoriza, JM., Borriello, L., et al.[2023]

The tumor microenvironment (TME) is crucial for understanding cancer progression and treatment response, as it consists of various cells and molecules that interact with tumor cells.

Novel non-invasive imaging techniques are needed to better characterize the TME, which can improve early diagnosis, guide biopsies, monitor therapies, and help develop new treatments tailored to individual patients' tumor compositions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Molecular Imaging of the Tumour Microenvironment. Foray, C., Barca, C., Backhaus, P., et al.[2021]

Non-invasive imaging techniques, such as PET, MRI, and optical imaging, can provide crucial insights into the tumor microenvironment, helping to assess cancer aggressiveness, metastasis, and treatment response.

Current research is focused on imaging specific features of the tumor microenvironment, like inflammation and hypoxia, which can guide the development of new treatments and improve patient monitoring in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging the Tumor Microenvironment. Abadjian, MZ., Edwards, WB., Anderson, CJ.[2018]

Tamoxifen treatment in MCF7 human breast tumors led to rapid necrosis of tumor cells, indicating its potential to inhibit blood vessel growth (angiogenesis) and promote tumor regression.

Imaging techniques revealed that after tamoxifen treatment, there was a significant increase in ATP levels, suggesting enhanced energy metabolism in the tumor's reparative fibrous tissue, which may play a role in the tumor's response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and spectroscopy of MCF7 human breast cancer: pathophysiology and monitoring of treatment. Degani, H., Furman, E., Fields, S.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging and blood oxygenation level-dependent magnetic resonance imaging for the assessment of changes in tumor biology with treatment. [2015]

3. Italy pubmed.ncbi.nlm.nih.gov

The role of magnetic resonance imaging in oncology. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Janus-faced tumor microenvironment and redox. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Multimodal Molecular Imaging of the Tumour Microenvironment. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Imaging the Tumor Microenvironment. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and spectroscopy of MCF7 human breast cancer: pathophysiology and monitoring of treatment. [2019]