Evaluation of Changes in the Immunological Microenvironment Surrounding Subcutaneous Breast Cancer Metastases After Liquid Nitrogen Cryotherapy (CRIMCAS)

Evaluation of Changes in the Immunological Microenvironment Surrounding Subcutaneous Breast Cancer Metastases After Liquid Nitrogen Cryotherapy: Descriptive Pilot Study.

Cryotherapy is a cold ablation technique used in many tumor locations. The destruction of tissues by cryoablation preserves proteins and in particular anti-tumor antigens, which could induce the stimulation of an immune response. Compared to other interventional radiology techniques, cryotherapy induces a higher immunogenic response. Studies describe complex responses with elevated levels of activating NK cells, circulating and anti-tumor T cells, and pro-inflammatory and NF-KB dependent cytokines.

In breast cancer, whether or not an immune response is triggered depends on the type of cryoablation used. Indeed, high intensity cryoablation (rapid freezing in one cycle of the entire tumor volume) seems to induce a tumor-specific immunodestructive response, whereas low frequency cryoablation (several small repetitive cycles until a sufficient volume of ice is obtained) does not induce an immunogenic response and can even induce an immunoregulation with immunotolerance of the tumor cells The University Hospital of Nîmes has recently acquired a new liquid nitrogen cryotherapy technique, more powerful than the one classically performed with Argon. This technique is used for palliative and analgesic purposes in patients with metastatic breast cancer presenting painful subcutaneous metastases. The aim of this study is to evaluate in these patients the changes in the tumor microenvironment and the immune response potentially induced by this very high intensity cryotherapy.

The study investigators hypothesize that locoregional treatment with liquid nitrogen cryotherapy of subcutaneous breast cancer metastases will allow a systemic response through the induction of an immune response. A better understanding of the type of immune response induced will allow the development of combined therapeutic strategies with curative and not only palliative and analgesic aims.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Cryotherapy treatment

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julien Frandon; Phone Number: 04.66.68.67.22; Email: julien.frandon@chu-nimes.fr

Study Locations

• France
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Sub-Investigator: Nadine Houede
    • Sub-Investigator: Jean-Paul Beregi
    • Principal Investigator: Julien Frandon
    • Contact: Anissa Megzari; Phone Number: 04.66.68.34.00; Email: drc@chu-nimes.fr
    • Sub-Investigator: Frédéric Fiteni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient must have given their free and informed consent
• The patient must be a member or beneficiary of a health insurance plan
• Patient with metastatic breast cancer with painful subcutaneous metastases.
• Patient eligible for cryotherapy.
• Therapeutic decision of antalgic and palliative treatment by cryotherapy taken in Pluridisciplinary Consultation Meeting.
• Patient available for 15-day follow-up.

Exclusion Criteria:

• The subject is in a period of exclusion determined by a previous study
• The subject us unable to express their consent or refuses to sign the consent form
• The patient is under safeguard of justice or state guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryotherapy	Procedure: Cryotherapy treatment; Cryotherapy treatment administered by an interventional radiologist: the cryotherapy needle is placed under local anesthesia, ultrasound monitoring in real time. A complete cryotherapy cycle is performed with: freezing until the entire tumor is frozen as judged by ultrasound, then thawing for the same duration and refreezing according to the same principle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the immunological makeup of the tumor before liquid nitrogen cryotherapy treatment	Cytometry by Time Of Flight (CyTOF®) mass cytometry analysis of biopsy samples to identify lymphocyte and macrophage populations and anti-tumor markers	Day 0
Description of the immunological makeup of the tumor after liquid nitrogen cryotherapy treatment	Cytometry by Time Of Flight (CyTOF®) mass cytometry analysis of biopsy samples to identify lymphocyte and macrophage populations and anti-tumor markers	Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' tolerance to cryotherapy treatment	Scoring of complications and adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria	Day 15
Level of pain related to subcutaneous metastases before cryotherapy treatment	0-10 Visual analog scale	Day 0 immediately before cryotherapy treatment
Level of pain related to subcutaneous metastases after cryotherapy treatment	0-10 Visual analog scale	Day 0 immediately after cryotherapy treatment
Level of pain related to subcutaneous metastases after cryotherapy treatment	0-10 Visual analog scale	Day 15
Pain related to subcutaneous metastases before cryotherapy treatment	Brief Pain Inventory (BPI): score from 0-120	Day 0 immediately before cryotherapy treatment
Pain related to subcutaneous metastases after cryotherapy treatment	Brief Pain Inventory (BPI): score from 0-120	Day 0 immediately after cryotherapy treatment
Pain related to subcutaneous metastases after cryotherapy treatment	Brief Pain Inventory (BPI): score from 0-120	Day 15
Patient reported quality of before cryotherapy treatment	European Organisation for Research and Treatment of Cancer - C30 (EORTC QLQ-C30). This questionnaire is composed of 30 items grouped into 15 scales. A good quality of life is associated with a high score for the functional scales and a low score for the symptom scales	Day 0
Patient reported quality of after cryotherapy treatment	European Organisation for Research and Treatment of Cancer - C30 (EORTC QLQ-C30). This questionnaire is composed of 30 items grouped into 15 scales. A good quality of life is associated with a high score for the functional scales and a low score for the symptom scales	Day 15

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Julien Frandon, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: cryotherapy; cytotoxicity
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: EMERGENCE GSO/2020/JF-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No