To Detect Cryoimmunologic Response Induced by Early Breast Cancer Ultrasound-guided Cryoablation (ICE-study)

NCT05727813 | Completed DMC

• 1 other identifier: URomLS Prot.0930/2021Rif. 6528
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of our study is to examine the cryoimmunologic response and its mechanisms induced by US-guided cryoablation of small breast tumors (\<2 cm) not eligible to neoadjuvant therapy. We will recruit 30 women who will undergo cryoablation and their results will be compared with a control group of 30 women, who will follow the same therapeutic pathway without performing cryoablation. All recruited patients will undergo an enrollment check, pre-cryoablation breast MRI and blood test to assess immune response, breast cancer US-guided cryoablation, post-cryoablation breast MRI and the same blood test to evaluate immunologic response. Within 21 days all patients will undergo breast surgery, with immuno-histopathological analysis on surgical specimen. At least 10 days after surgery the patient will undergo clinical breast examination, blood test to assess immune response and patient satisfaction questionnaire. Cryoablation treatment will be performed using a 14G cryoprobe under us-guidance for visualization of the ice ball surrounding the lesion. The ultrasound guide is used to ensure that the action affects the entire tumor and that therapeutic temperatures are reached in every part of the tumor. Pre- and post- cryoablation breast MRI will be performed on a 3T magnet to assess cryoablation rate of success. Artificial intelligence algorithms will also be used for this purpose. Cryoablation treatment efficacy will also be evaluated with ultrasound. The immunological fitness of cancer patients will be studied by flow cytometry, evaluating the presence of cytokines/chemokines relevant during anticancer immune response/tumor progression and for the presence of molecules released by cells during an immunogenic cell death. The goal of our study will be to demonstrate that cryoablation of breast cancer can induce an antitumor immune response. Therefore this approach could become an additional tool in the oncological treatment of breast cancer.

Conditions

Cancer, Treatment-Related; Tumor of Breast; Systemic Inflammatory Response; Stage I Breast Cancer

Keywords

breast cancer treatment; Breast imaging evaluation; immunologic response; cryotherapy

Outcome Measures

Primary Outcomes (5)

• Immunogenic Cell Death induced by tumor cryoablation, cytokines

  Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4)

  12 months

• Immunogenic Cell Death induced by tumor cryoablation, pro-inflammatory cytokines

  Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α),

  12 months

• Immunogenic Cell Death induced by tumor cryoablation, immunosuppressive cytokines

  Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: immunosuppressive cytokines (TGF-β1, IL-10, PGE2),

  12 months

• Immunogenic Cell Death induced by tumor cryoablation, chemokines

  Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin),

  12 months

• Immunogenic Cell Death induced by tumor cryoablation, ATP and HMGB1

  Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: ATP and HMGB1 are molecules released in the serum by cancer cells during immunogenic cell death.

  12 months

Secondary Outcomes (3)

• Rate of complete response

  12 months

• Cryoablation treatment capability to induce immunogenic tumor cell death, specimen

  12 months

• safety margin of Cryoablation treatment

  12 months

Study Arms (2)

cryoablation

EXPERIMENTAL

We will enroll women with a biopsy-proven diagnosis of early-stage breast cancer (T1 N0), not eligible for neo-adjuvant therapy, scheduled to breast surgery (mastectomy or nodulectomy), who have given the informed consent for the study. We will recruit 20 women who will undergo cryoablation.

Device: cryoablation

no cryoablation

NO INTERVENTION

The results will be compared with those obtained from a control group of 20 women, who will follow the same therapeutic pathway for the treatment of breast cancer without performing cryoablation.

Interventions

cryoablation DEVICE

cryoablation of breast cancer smaller than 2 cm

cryoablation

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: female breast cancer patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 year-old women with needle (14-20 G) biopsy-proven invasive breast cancer. The specimens taken are adequate for tumor classification and receptors analysis;
• imaging (ultrasound and magnetic resonance imaging) confirmed single \<2 cm breast cancer;
• clearly visible lesion on ultrasound with a minimum distance of 1 cm between the tumor and the skin and 2 cm between the tumor and the nipple;
• not eligible patients for neo-adjuvant therapy;
• patients who are scheduled for breast cancer surgical resection (lumpectomy or mastectomy) after cryoablation; stage I disease: T1 N0;

You may not qualify if:

• DCIS without invasive components on the core biopsy;
• Tamoxifen, aromatase inhibitors and neoadjuvant chemotherapy within 30 days prior to Visual-ICE treatment;
• XRT or previous ablative therapy to the affected breast;
• distance \<1 cm between the tumor and the skin, the nipple or the chest wall;
• microcalcifications as the only evidence of breast cancer on imaging;
• breast implants;
• severe cardiac or cerebrovascular disease;
• pregnancy, nursing or puerperium;
• patients with a general health status ASA\> 2, which includes in a non-limiting way patients suffering from renal dysfunction due to hepatorenal syndrome or who are in the perioperative period for liver transplantation;
• active and ongoing infection, e.g. urinary tract infection, respiratory tract infection and other known infections;
• poor blood glucose control;
• severe hypertension;
• any contraindications for Visual-ICE ablation therapy;
• sleep apnea syndrome

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Sapienza University of Rome

Roma, 00161, Italy

Location

Related Publications (4)

• Sabel MS, Nehs MA, Su G, Lowler KP, Ferrara JL, Chang AE. Immunologic response to cryoablation of breast cancer. Breast Cancer Res Treat. 2005 Mar;90(1):97-104. doi: 10.1007/s10549-004-3289-1.

  PMID: 15770533 RESULT

• Mauri G, Sconfienza LM, Pescatori LC, Fedeli MP, Ali M, Di Leo G, Sardanelli F. Technical success, technique efficacy and complications of minimally-invasive imaging-guided percutaneous ablation procedures of breast cancer: A systematic review and meta-analysis. Eur Radiol. 2017 Aug;27(8):3199-3210. doi: 10.1007/s00330-016-4668-9. Epub 2017 Jan 3.

  PMID: 28050693 RESULT

• McArthur HL, Diab A, Page DB, Yuan J, Solomon SB, Sacchini V, Comstock C, Durack JC, Maybody M, Sung J, Ginsberg A, Wong P, Barlas A, Dong Z, Zhao C, Blum B, Patil S, Neville D, Comen EA, Morris EA, Kotin A, Brogi E, Wen YH, Morrow M, Lacouture ME, Sharma P, Allison JP, Hudis CA, Wolchok JD, Norton L. A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling. Clin Cancer Res. 2016 Dec 1;22(23):5729-5737. doi: 10.1158/1078-0432.CCR-16-0190. Epub 2016 Aug 26.

  PMID: 27566765 RESULT

• Galati F, Pasculli M, Maroncelli R, Rizzo V, Moffa G, Cerbelli B, d'Amati G, Catalano C, Pediconi F. Ultrasound-guided cryoablation of early breast cancer: safety, technical efficacy, patients' satisfaction, and outcome prediction with MRI/CEM: a pilot case-control study. Eur Radiol Exp. 2024 Oct 22;8(1):120. doi: 10.1186/s41747-024-00515-4.

  PMID: 39436590 DERIVED

MeSH Terms

Conditions

Neoplasms, Second Primary; Breast Neoplasms

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Federica Pediconi, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Federica Pediconi

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: February 14, 2023
• Study Start: September 1, 2022
• Primary Completion: January 16, 2023
• Study Completion: January 27, 2023
• Last Updated: February 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)