Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Control arm: Stage I/II TNBC patients will receive neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.

Cryoablation Alone Arm: Intervention with cryoablation alone followed by neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.

Cryoablation + PD1 Inhibitor Arm: Intervention with cryoablation + Pembrolizumab followed by neoadjuvant chemotherapy followed by lumpectomy/mastectomy with sentinel node biopsy +/- axillary dissection.

Tumor ablation before neoadjuvant chemotherapy

Cryoablation

Combination of cryoablation with PD1 inhibitor before neoadjuvant chemotherapy

Cryoablation combined with PD1 Inhibitor

Rakhshanda Layeequr Rahman, MD

Sharda Singh, PHD

Summary Points:

1. High Risk Breast Cancers: Triple negative cancer is considered high risk due to high rate of local and systemic failure. Newer innovative treatment strategies are needed to improve systemic control of disease and survival.
2. Immune system modulation: is an emerging modality in cancer treatment. Tumor antigens can stimulate T cells to identify and destroy cancer cells. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. This concept is precisely applicable to triple negative breast cancer due to their antigenicity. Checkpoint inhibitors are an attractive method for treatment of high-risk breast cancers. However, to leverage the efficacy of checkpoint inhibition, approaches are needed to enhance delivery of cancer antigens to the T cells.
3. Cryoablation: offers an efficacious and safe method to enhance tumor antigen presentation to the immune cells while destroying the primary tumor. This ablation method is superior by virtue of antigen preservation in situ despite toxicity to the tumor cell. Impact of cryoablation in enhancing immunological responses in tumor microenvironment are well established; however, cryoablation can also cause tumor antigen tolerance via non-specific stimulation of T cells.
4. Rationale for combining cryoablation and checkpoint inhibitors: Since checkpoint inhibitors curtail the tolerance developed by tumor antigens, and cryoablation enhances antigen presentation and T cell recruitment, it is intuitive that combination of these two approaches presents an ideal opportunity to leverage the benefits of both approaches while curtailing the limitations of either. Therefore, the investigators hypothesize in this study that their combination will improve the response rate and the degree of response.

Since proposed intervention ( cryoablation and immune therapy infusion) cannot be masked with placebo, only the data analyst will be masked.

Grouping Immune-modulation With Cryoablation (LOGIC) for Breast Cancers

Local Therapy Optimization by Grouping Immune-modulation With Cryoablation (LOGIC) for High Risk Breast Cancers

Pathological analysis of tumor after completion of local and neoadjuvant therapy

All tissue specimens that undergo routine pathology reporting will be evaluated for TIL score at baseline and at lumpectomy after systemic therapy. TIL score will be reported according to guidelines put forth by the International TILs Working Group. We hypothesize that percent TIL score will increase by 30% from baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Grouping Immune-modulation With Cryoablation (LOGIC) for Breast Cancers	NCT05806385	Triple Negative...	Cryoablation Cryoablation co...	18 Years - 90 Years	Texas Tech University Health Sciences Center
Grouping Immune-modulation With Cryoablation (LOGIC) for Breast Cancers	NCT05806385	Triple Negative...	Cryoablation Cryoablation co...	18 Years - 90 Years	Texas Tech University Health Sciences Center

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