Immune Therapy + Cryoablation for Breast Cancer

Recruiting at 2 trial locations

Overseen By Meredith Carter, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, Corticosteroids, others

Disqualifiers: Autoimmune disease, Hepatitis B/C, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for women with triple-negative breast cancer. Researchers aim to determine if a freezing technique called cryoablation, combined with immune therapy drugs (Ipilimumab and Nivolumab), improves the likelihood of remaining cancer-free for three years. Participants should have breast cancer that hasn't spread and should be planning surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to advancements in breast cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it prohibits the chronic use of immunosuppressants and systemic corticosteroids. Brief steroid use is allowed for certain conditions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ipilimumab and nivolumab is generally well-tolerated in cancer treatments. Studies have found that this combination can lead to positive results in various cancers. However, some patients might experience side effects like tiredness, skin rash, or diarrhea. In some cases, these side effects can be more serious but are manageable with medical care.

For cryoablation, which involves freezing cancer cells, research suggests it is safe for breast cancer patients. Most reported side effects are minor, such as bruising or slight pain at the treatment site.

Overall, both treatments have been shown to be safe, but like all medical treatments, they may have side effects. Discuss potential risks with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combined use of Ipilimumab and Nivolumab for breast cancer because these drugs harness the power of the immune system to fight cancer cells. Unlike traditional treatments like chemotherapy and hormone therapy, which directly attack cancer cells, these drugs are immune checkpoint inhibitors that target and block proteins used by cancer cells to avoid immune detection. This innovative approach can potentially lead to more targeted and effective results, with fewer side effects, as the immune system itself works to eliminate the cancer. Furthermore, the combination with cryoablation, a technique that freezes and destroys cancer cells, could enhance the treatment's effectiveness by releasing more tumor antigens and boosting the immune response.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will evaluate two different treatment combinations for breast cancer. One group of participants will receive Ipilimumab and Nivolumab. Research has shown that these drugs may help treat certain cancers by increasing survival rates and improving response to treatment, especially in challenging cases like metaplastic breast cancer. This suggests potential effectiveness for triple-negative breast cancer as well.

Another group will receive Pembrolizumab. Both groups will also undergo Cryoablation, which has successfully controlled breast tumors, achieving a 90% success rate in completely destroying them. Cryoablation works by freezing and killing cancer cells and is particularly useful for both early-stage and advanced breast cancer. Together, these treatments offer hope for fighting triple-negative breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Heather McArthur, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with triple-negative breast cancer that's operable and hasn't spread far. They should have finished certain chemo, be able to undergo surgery, and not have other serious health issues or recent cancers. Participants must use birth control if needed and pass specific blood tests.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

I am scheduled for a total mastectomy or lumpectomy.

Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol

Exclusion Criteria

You have taken any experimental medications within 3 weeks before starting this treatment.

You have an ongoing autoimmune condition that needed medication in the last 2 years.

I do not have any health or mental conditions that could make this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive pre-operative cryoablation and immune checkpoint inhibition (ICI) with Pembrolizumab or Ipilimumab and Nivolumab

4-6 weeks

Surgery

Participants undergo either mastectomy or breast conserving surgery

1 week

Post-operative Treatment

Participants receive post-surgery Pembrolizumab or Nivolumab

up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Core Biopsy/Cryoablation
• Ipilimumab+Nivolumab

Trial Overview The study is testing the combination of a freezing technique called cryoablation with drugs Pembrolizumab, Ipilimumab, or Nivolumab before surgery. The goal is to see how this affects survival without cancer worsening within three years after treatment.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 5 Interventions

Pembrolizumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery pembrolizumab OR Ipilimumab and Nivolumab + Core Biopsy/Cryoablation + Breast Surgery +Post Surgery Nivolumab

Ipilimumab+Nivolumab is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Yervoy + Opdivo for:

• Melanoma
• Renal Cell Carcinoma
• Colorectal Cancer
• Hepatocellular Carcinoma
• Non-Small Cell Lung Cancer

Approved in European Union as Yervoy + Opdivo for:

• Melanoma
• Renal Cell Carcinoma
• Colorectal Cancer
• Non-Small Cell Lung Cancer
• Malignant Pleural Mesothelioma

Approved in Japan as Yervoy + Opdivo for:

• Melanoma
• Renal Cell Carcinoma
• Non-Small Cell Lung Cancer

Approved in Canada as Yervoy + Opdivo for:

• Melanoma
• Renal Cell Carcinoma
• Colorectal Cancer
• Non-Small Cell Lung Cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Monica Mita

Lead Sponsor

Trials

3

Recruited

100+

Heather McArthur

Lead Sponsor

Trials

1

Recruited

80+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

American Society of Clinical Oncology

Collaborator

Trials

40

Recruited

148,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Cryoablation is a minimally-invasive technique that effectively targets and destroys small breast cancers and metastatic disease, leading to shorter hospital stays and quicker recovery compared to traditional surgery.

Research suggests that cryoablation may enhance the effectiveness of immunotherapy by increasing the expression of tumor-specific antigens, potentially leading to a stronger immune response against cancer cells when used in combination with immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the use of cryoablation and immunotherapy for breast cancer. Olagunju, A., Forsman, T., Ward, RC.[2022]

In a pilot study involving 19 women with operable breast cancer, preoperative cryoablation and/or ipilimumab were found to be safe and well-tolerated, with no delays in planned mastectomy surgeries.

The combination of cryoablation and ipilimumab led to significant immune activation, including increased levels of certain T cells and cytokines, suggesting a potential for enhanced antitumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling. McArthur, HL., Diab, A., Page, DB., et al.[2022]

Cryoablation is a safe and well-tolerated outpatient procedure that can treat small breast cancers and metastatic sites, especially in patients who cannot undergo surgery.

Recent studies indicate that cryoablation may enhance the immune system's ability to recognize and attack cancer cells by increasing the expression of tumor neoantigens, potentially improving the effectiveness of immunotherapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryoablation and Immunotherapy for Breast Cancer: Overview and Rationale for Combined Therapy. Regen-Tuero, HC., Ward, RC., Sikov, WM., et al.[2021]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

Cryoablation is gaining popularity as a primary treatment for localized cancers and as a salvage therapy for metastatic cancers, showing promise in inducing a systemic antitumor immune response.

To enhance the immune response triggered by cryoablation, combining it with other immunomodulatory agents could create a more effective cryoimmunotherapeutic strategy, potentially improving outcomes for patients with metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer immunotherapy using tumor cryoablation. Sidana, A.[2014]

Cryoablation is a promising alternative to traditional surgery for breast cancer, as it is less invasive, preserves tumor antigens, and may enhance immune responses against distant metastases.

Combining cryoablation with immune checkpoint inhibitors (ICIs) could maximize the immunological benefits in high-risk breast cancer patients, and current clinical trials are exploring this combination to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leveraging cryoablation and checkpoint inhibitors for high-risk triple negative breast cancer. Sardela de Miranda, F., Castro, M., Remmert, N., et al.[2023]

In a study of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

A 58-year-old male with malignant melanoma experienced multiple immune-related adverse events (irAEs) after treatment with nivolumab and ipilimumab, highlighting the potential risks associated with immune checkpoint inhibitors.

The patient developed destructive thyroiditis, aseptic meningitis, and isolated ACTH deficiency, which required hormone replacement therapies, emphasizing the need for careful monitoring of patients undergoing treatment with these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: A Variety of Immune-Related Adverse Events Triggered by Immune Checkpoint Inhibitors in a Subject With Malignant Melanoma: Destructive Thyroiditis, Aseptic Meningitis and Isolated ACTH Deficiency. Katakura, Y., Kimura, T., Kusano, T., et al.[2023]

Immune checkpoint blockade (ICB) targeting PD-1 or PD-L1 has shown significant clinical activity in breast cancer, particularly in the triple-negative subtype and in earlier treatment lines, with some patients experiencing durable responses even in metastatic disease.

Current research is focused on enhancing the effectiveness of ICB by converting 'cold' tumors into 'hot' tumors through strategies that improve the tumor microenvironment, expand anti-tumor T cells, and enhance antigen presentation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of immune checkpoint blockade in breast cancer. Pellegrino, B., Tommasi, C., Cursio, OE., et al.[2022]

In a phase 3 trial involving 906 patients with resected advanced melanoma, nivolumab demonstrated a significantly higher 12-month recurrence-free survival rate of 70.5% compared to 60.8% for ipilimumab, indicating it is more effective as adjuvant therapy.

Nivolumab also had a much lower incidence of severe treatment-related adverse events (14.4%) compared to ipilimumab (45.9%), suggesting it is a safer option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. Weber, J., Mandala, M., Del Vecchio, M., et al.[2023]

Checkpoint immunotherapy is being explored as a new treatment for metastatic breast cancer, but single-agent therapies targeting PD1/PD-L1 or CTLA-4 have shown limited effectiveness.

Combining immunotherapy with other treatments like chemotherapy, radiotherapy, and targeted therapies may enhance cancer immunity and improve treatment outcomes, with ongoing clinical trials investigating these combination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer. Liu, ZB., Zhang, L., Bian, J., et al.[2020]

Nivolumab combined with ipilimumab significantly improves treatment outcomes in cancer, showing higher rates of complete response (CR), partial response (PR), and overall response rate (ORR) compared to either drug alone, based on a meta-analysis of 11 studies.

While the combination therapy N1I3 (1 mg/kg nivolumab and 3 mg/kg ipilimumab) was more effective than N3I1 (3 mg/kg nivolumab and 1 mg/kg ipilimumab), it also had a higher incidence of serious adverse events, though overall safety was still considered acceptable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis. Chen, J., Li, S., Yao, Q., et al.[2021]

Recent studies suggest that immune checkpoint inhibition (ICI) could be a promising treatment for breast cancer, particularly in early-stage and curable cases, as evidenced by encouraging results from phase III trials in triple-negative breast cancer.

Key biomarkers like tumor-infiltrating lymphocytes and PD-L1 expression are being explored to predict which patients may respond best to ICI, highlighting the need for further research on treatment strategies and patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating immunotherapy in the (neo)adjuvant setting of early breast cancer. Chan, JJ., Tan, TJY., Dent, RA.[2021]

Ipilimumab is a monoclonal antibody that enhances T cell activation by blocking the CTLA-4 receptor, leading to improved antitumor responses and has been shown to increase overall survival in patients with advanced melanoma, a condition with a poor prognosis.

While ipilimumab has demonstrated significant efficacy, it can cause serious immune-related adverse effects that require prompt management, highlighting the importance of monitoring patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Graziani, G., Tentori, L., Navarra, P.[2020]

A systematic review of 14 randomized controlled trials found that combining nivolumab (NIVO) with ipilimumab (IPI) significantly increases the risk of treatment-related adverse events (TRAEs) compared to NIVO alone, with an overall risk ratio of 1.11 for any grade TRAEs and 1.95 for severe (grade 3 or 4) TRAEs.

Specific adverse events were notably higher with the combination therapy, including colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68), indicating that while the combination may be effective, it comes with increased safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. Kamat, S., Patel, J., Brown, BR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11912063/

Cryoablation for breast cancer: a narrative review of ... Cryoablation has been proven to be a unique and effective approach for treating early-stage, advanced, and inoperable breast cancer patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11452421/

ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor ... This study demonstrates cryoablation to be safe for early-stage breast cancer ≤ 1.5 cm, with minor adverse events (such as bruising, minor ...

3. icecure-medical.com icecure-medical.com/blog/cryoablation-for-breast-cancer-evidence-to-date/

Cryoablation for Breast Cancer - Evidence to date Cryoablation was found to be safe, with only minor adverse events reported. During a median 2-year follow-up, 6.36% of patients experienced true ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1469684/full

Cryoablation in the treatment of early breast cancer In breast cancer, cryoablation has demonstrated a complete ablation rate of 90%, indicating its effectiveness in achieving tumor control without ...

5. ajronline.org ajronline.org/doi/10.2214/AJR.24.31392

Cryoablation of Primary Breast Cancer in Patients Ineligible ... The purpose of this study was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for ...

6. link.springer.com link.springer.com/article/10.1007/s12609-024-00561-2

Cryoablation and Breast Disease Cryoablation is safe, effective, and well tolerated by patients. Cryoablation is being increasingly utilized to treat a subset of patients with ...