Immune Therapy + Cryoablation for Breast Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after taxane-based neoadjuvant chemotherapy.
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.
What data supports the effectiveness of the treatment Immune Therapy + Cryoablation for Breast Cancer?
Research shows that combining immune checkpoint inhibitors like ipilimumab and nivolumab can enhance the immune response against tumors, as seen in other cancers like melanoma. Additionally, combination strategies in breast cancer are being explored to improve outcomes by making tumors more responsive to immunotherapy.12345
Is the combination of immune therapy drugs nivolumab and ipilimumab generally safe for humans?
The combination of nivolumab and ipilimumab can increase the risk of side effects like colitis (inflammation of the colon), pneumonitis (lung inflammation), and diarrhea compared to using nivolumab alone. Some patients have experienced serious immune-related side effects affecting various organs, so it's important to monitor for these reactions during treatment.678910
How is the treatment of Ipilimumab+Nivolumab with cryoablation unique for breast cancer?
This treatment combines cryoablation, which uses extreme cold to destroy tumors and enhance immune response, with immune therapy drugs Ipilimumab and Nivolumab to boost the body's ability to fight cancer. This approach is unique because it aims to improve the effectiveness of immunotherapy in breast cancer, which typically has a limited response to such treatments.1112131415
Eligibility Criteria
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
See 12 more
Exclusion Criteria
You have taken any experimental medications within 3 weeks before starting this treatment.
I do not have any health or mental conditions that could make this study unsafe for me.
I regularly take medication to suppress my immune system.
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- Core Biopsy/Cryoablation (Procedure)
- Ipilimumab+Nivolumab (Checkpoint Inhibitor)
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment ArmExperimental Treatment5 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cedars Sinai Medical CenterLos Angeles, CA
Ohio State University Medical CenterColumbus, OH
UT Southwestern Medical CenterDallas, TX
Providence Cancer InstitutePortland, OR
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
Monica MitaLead Sponsor
Heather McArthurLead Sponsor
Boston Scientific CorporationIndustry Sponsor
Susan G. Komen Breast Cancer FoundationCollaborator
American Society of Clinical OncologyCollaborator
Bristol-Myers SquibbIndustry Sponsor
Memorial Sloan Kettering Cancer CenterCollaborator
References
Integrating immunotherapy in the (neo)adjuvant setting of early breast cancer. [2021]Breast cancer is a relative latecomer in the success story of immuno-oncology. In this review, we focus on the preclinical and clinical lines of evidence to justify the evaluation of immune checkpoint inhibition (ICI) for the curative-intent treatment of breast cancer, the latest and ongoing trials of (neo)adjuvant immunotherapy, and practical considerations in clinical practice associated with this new treatment paradigm.
A review of immune checkpoint blockade in breast cancer. [2022]In the recent years characterized by the cancer immunotherapy revolution, attention has turned to how to potentially boost and/or generate an efficient anti-tumor immune response in breast cancer (BC). Clinical activity of immune checkpoint blockade (ICB) targeting PD-1 or PD-L1 in BC has been more evident in the triple negative subtype and in earlier lines of the treatment. Remarkably, some responders to single agent ICB have achieved durable responses with metastatic disease, possibly as a result of treatment-induced immunological memory. However, most BC are immunologically quiescent and current research efforts developing ICB combinations are attempting to convert "cold" into "hot" tumors by manipulating the tumor microenvironment, expanding anti-tumor T cells improving efficient antigen presentation, and suppressing pro-tumor inhibitory cells. The aim of this review is to summarize existing data on the efficacy of immune checkpoint blockers as single agents and combination strategies in all BC subtypes, highlighting the BC subgroups that benefit most from ICB.
Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. [2023]Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.
Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. [2020]Ipilimumab (Yervoy, developed by Medarex and Bristol-Myers Squibb) is a fully human monoclonal IgG1κ antibody against the cytotoxic T-lymphocyte antigen-4 (CTLA-4), an immune-inhibitory molecule expressed in activated T cells and in suppressor T regulatory cells. Interaction of the monoclonal antibody with CTLA-4 blocks inhibitory signals generated through this receptor and enhances T cell activation, leading to increased antitumor responses. Ipilimumab has been approved by FDA in March 2011 as monotherapy (3mg/kg every 3 weeks for 4 doses) for the treatment of advanced (unresectable or metastatic) melanoma both in pre-treated or chemotherapy naïve patients. Four months later, ipilimumab has received a rapid approval by the European Commission, after a positive opinion from the Committee for Medicinal Products for Human Use. However, the indication in the EU is limited to previously-treated patients with advanced melanoma. Ipilimumab is the first agent that has demonstrated to improve overall survival in patients with metastatic melanoma, which has a very poor prognosis, in randomized phase III clinical trials. The patterns of tumour response to ipilimumab differ from those observed with cytotoxic chemotherapeutic agents, since patients may have a delayed yet durable response and obtain long-term survival benefit despite an initial tumour growth. The major draw-back of ipilimumab is the induction of immune-related adverse effects; the latter can be life-threatening, unless promptly managed with immunosuppressive agents (most frequently corticosteroids) according to specific guidelines. Further development of ipilimumab includes its use in the neoadjuvant or adjuvant high-risk melanoma setting and for the treatment of other refractory and advanced solid tumours, either as single agent or in combination with additional immunostimulating agents or molecularly targeted therapies.
Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer. [2020]Checkpoint immunotherapy is emerging as a new therapeutic approach for metastatic breast cancer. Monotherapy of immunoagents against PD1/PD-L1 or CTLA-4 has shown little efficacy in these patients. Recently, to determine the optimal use of immunotherapy, there has been a rapid expansion in the number of clinical trials developing immunotherapy combinations. These combination therapeutic approaches can enhance various aspects of cancer immunity, such as tumor antigenicity or intratumor T cell infiltration, which provides a theoretical basis for combining them with checkpoint immunotherapy to achieve synergistic effects. Here, we review the available data and ongoing efforts to establish the safety and efficacy of immunoagents in combination with chemotherapy, radiotherapy, HER2-targeted therapy, CDK4/6 inhibitors, PARP inhibitors, and another checkpoint immunoagents.
Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. [2022]A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to examine treatment-related adverse events (TRAEs) for combination of nivolumab (NIVO) and ipilimumab (IPI) compared to NIVO monotherapy among cancer patients. We searched several databases to identify relevant RCTs. Meta-analysis was performed using random-effects model. In fourteen RCTs included in the study, we found that compared to NIVO monotherapy, combination NIVO + IPI increased the risk of any grade (Risk Ratio (RR) = 1.11), and grade 3 or 4 (RR = 1.95) TRAEs. Compared to NIVO, NIVO + IPI had higher risk for any grade colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68).
Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).
Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. [2019]There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab.
The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis. [2021]Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab plus ipilimumab therapy in cancer treatment.
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. [2023]Recently, immune checkpoint inhibitors have been drawing much attention as cancer immunotherapy, but it has been shown that various immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors in various organs, which has become one of the serious issues at present. A 58-year-old Japanese male with malignant melanoma was treated with nivolumab and/or ipilimumab. During the period of treatment, he suffered from various irAEs. Firstly, about 1 month after starting nivolumab monotherapy, destructive thyroiditis was induced, and so we started replacement therapy with levothyroxine. Secondly, about 1 month after starting nivolumab and ipilimumab combination therapy, aseptic meningitis was induced. We stopped both drugs and started steroid therapy with prednisolone. Finally, about 9 months after restarting nivolumab, isolated adrenocorticotropic hormone (ACTH) deficiency was induced, and so we started replacement therapy with hydrocortisone. Taken together, we should bear in mind the possibility of a variety of irAEs when we use immune checkpoint inhibitors.
Leveraging cryoablation and checkpoint inhibitors for high-risk triple negative breast cancer. [2023]Breast cancer is the second most common cancer among women in the United States in which the standard of care treatment is surgery with adjunctive therapy. Cryoablation, which destroys the tumor using extremely cold temperatures while preserving the potential tumor antigens, is a promising alternative to surgical resection. It is less invasive, cosmetically appeasing, cost-effective, and capable of contributing to the abscopal effect - the immune response targeting potential distant metastasis. However, to maximize the immunologic benefit of cryoablation in biologically high-risk breast cancers, combination with therapies that enhance immune activation, such as immune checkpoint inhibitors (ICIs) may be necessary. This mini review describes the fundamentals of cryoablation and treatment with ICIs, as well as discuss the caveats in both strategies and current clinical trials aimed to improve this approach to benefit patients.
Cryoablation and Immunotherapy for Breast Cancer: Overview and Rationale for Combined Therapy. [2021]Cryoablation is a well-tolerated outpatient procedure that has been used to treat metastatic sites as well as small breast cancers in patients who are considered poor candidates for surgery. Recent studies suggest that cell disruption caused by cryoablation may increase the expression and immunogenicity of tumor neoantigens, which could enhance the ability of the immune system to recognize and attack cancer cells at both local and distant sites. Such an approach might broaden the role of immunotherapy for the treatment of breast cancer, which has previously demonstrated limited response to these agents, likely owing to the modest immunogenicity of most breast cancer subtypes. If cryoablation can induce a systemic tumor-specific response, it could enhance tumor susceptibility to immunotherapy agents. This review briefly summarizes the necessary components for generating an immune response against tumor cells, reviews the tumor microenvironment of breast cancer, describes the rationale for and limitations of immune checkpoint inhibition, highlights the potential for cryoablation to induce a systemic tumor-specific immune response, and describes the rationale for combining cryoablation and immune checkpoint inhibitors for the treatment of breast cancer. Keywords: Ablation Techniques, Breast, Neoplasms-Primary, Percutaneous, Tumor Microenvironment, Tumor Response, Ultrasonography © RSNA, 2021.
A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling. [2022]To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer.
Cancer immunotherapy using tumor cryoablation. [2014]Cryoablation is increasingly being used as a primary treatment for localized cancers and as a salvage therapy for metastatic cancers. Anecdotal clinical reports and animal experiments have confirmed an induction of systemic antitumor immune response by tumor cryoablation. To capitalize on the stimulatory effects of cryoablation for cancer immunotherapy, this response must be intensified using other immunomodulatory agents. This article reviews the preclinical and clinical evidence and discusses the mechanism of the antitumor immune response generated by cryoablation. The rationale and evidence behind several immunotherapy approaches that can be combined with cryoablation to devise a cryoimmunotherapeutic strategy with a potential to impact the progression of metastatic disease are described.
An update on the use of cryoablation and immunotherapy for breast cancer. [2022]The use of cryoablation, a minimally-invasive image-guided technique to target and kill cancer cells, continues to gain traction within the medical field and with patients. This includes the use of cryoablation for the treatment of small breast cancers and focal sites of metastatic disease. In comparison to open surgical approaches, length of hospital stay and recovery time are decreased with the use of cryoablation. Research studies have also found that cryoablation may actually enhance tumor susceptibility to immunotherapy agents. Immunotherapy enhances a person's own immune system to identify and attack cancer cells. It is proposed that after cryoablation there is increased expression of tumor specific antigens which the body can recognize as foreign invaders and with the combination of immunotherapy, result in an even more robust and efficient attack on the cancer cells. In this review we aim to highlight some of the recent advances in cryoablation which support the potential for cryoablation to induce these tumor-specific immune responses and thus supporting the use of combining cryoablation and immunotherapy for the treatment of breast cancer.