Peritumoral and Periganglionic Infiltration of Levobupivacaine Prior to Conservative Surgery for Triple-negative Breast Cancer (EPPIL)

Breast cancer is one of the most common cancers among women. One in eight women in France will develop breast cancer during their lifetime (Inca). In 2023, 61,214 new cases of breast cancer were diagnosed in France, and in 2018, 12,146 deaths were attributed to this disease (e-cancer). Triple-negative breast cancer is characterised by the absence of hormone receptors (progesterone and oestrogen) and the HER2 protein on the surface of its cells. It is the breast cancer with the highest risk of recurrence, with a progression-free survival rate of 62% at 2 years (Di Lisa et al, 2023).

In vitro, local anaesthetics have been shown to have breast tumour cytotoxicity, according to Borgeat in 2012. Among the various local anaesthetics tested in vitro, levobupivacaine has been shown to have the highest breast tumour cytotoxicity, according to Zhi-Fu Wu in 2022. At doses below systemic toxicity thresholds and at concentrations routinely used, levobupivacaine induces greater apoptosis and reduces the metabolic activity of breast tumour cells to a greater extent than lidocaine. Levobupivacaine has an antitumour effect on MDA-MB-31 cells, according to Zhi-Fu Wu in 2022. MDA-MB-31 cells overexpress the voltage-gated sodium channel (VGSC). The VGSC is composed of different subunits, including the Nav1.5 α subunit, which can be inactivated by levobupivacaine.

In breast cancer, VGSC is mainly overexpressed in metastatic cancers and in the triple-negative line. The Nav1.5 α subunit of VGSC plays a role in tumour cell growth and migration. In vitro, a decrease in MDA-MB-231 cell migration has been demonstrated with levobupivacaine. Inactivation of Nav1.5 α with a molecule other than levobupivacaine (e.g., phenytoin) has shown antitumour effects in vitro and in vivo (Chen et al, 2022).

Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a commonly performed procedure within the scope of their marketing authorisation.

Badwe et al. (2023) demonstrated a benefit of peritumoral injection of 0.5% lidocaine on overall survival and progression-free survival in women with operable breast cancer. However, in this study, the type of surgery varied (lumpectomy or mastectomy) and only a peritumoral injection was performed (without periganglionic injection). Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented.

Targeting VGSC using a well-characterised local anaesthetic such as levobupivacaine could be a strategy for reducing the metastatic risk of triple-negative breast cancers, especially since surgical infiltration of local anaesthetics is a procedure commonly performed within the scope of their marketing authorisation.

Badwe et al. Furthermore, no specific analysis of the triple-negative breast cancer subgroup was presented.

Thus, no high-level evidence (prospective, randomised, double-blind) studies have been conducted on the benefits of peritumoral and periganglionic levobupivacaine infiltration in the context of conservative surgery (lumpectomy) for triple-negative breast cancer. The literature only contains in vitro studies, retrospective studies and a few rare prospective studies that were not conducted blind

Study Overview

• Status: Not yet recruiting
• Conditions: Triple-negative Breast Cancer
• Intervention / Treatment: Drug: LVB infiltration

Detailed Description

Objectives:

Primary: To study the interest of peritumoral and periganglionic infiltration of levobupivacaine prior to conservative surgery for triple-negative breast cancer on progression-free survival at 2 years.

Secondary:

• To study the interest of peritumoral and periganglionic infiltration of levobupivacaine prior to conservative surgery for triple-negative breast cancer on overall survival at 2 years.
• To study the interest of peritumoral and periganglionic infiltration of levobupivacaine prior to conservative surgery for triple-negative breast cancer on metastasis-free survival at 2 years.
• To study the interest of peritumoral and periganglionic infiltration of levobupivacaine prior to conservative surgery for triple-negative breast cancer on short- and long-term post-operative pain.
• To evaluate the tolerance of peritumoral and periganglionic infiltration of levobupivacaine prior to conservative surgery for triple-negative breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 760
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gestonnairedu / CURRS, /; Phone Number: 0326918822; Email: currs@univ-reims.fr

Study Locations

• France
  • Champagne-Ardenne
    • Reims, Champagne-Ardenne, France, 51100
      • Institut Godinot
      • Contact: Gestonnairedu / CURRS, /; Phone Number: 33 0326918822; Email: coralie.barbe1@univ-reims.fr

Participation Criteria

Eligibility Criteria

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

Description

This study will include women:

• with histologically confirmed triple-negative breast cancer
• who have undergone neoadjuvant chemotherapy, regardless of the protocol used
• eligible for conservative surgery with sentinel lymph node biopsy or axillary lymph node dissection for whom surgery is performed under general anaesthesia
• with a ECOG status of 0 or 1
• of legal age
• affiliated with a social security system
• agreeing to participate in the study

The following women will not be included in the study:

• those with a history of allergy to local anaesthetics, regardless of class
• those with metastatic breast cancer
• those undergoing lumpectomy for breast cancer with histology other than triple negative
• undergoing total mastectomy
• those for whom the surgery is a repeat of the initial surgery
• with a personal history of breast cancer having a personal history of cancer (other than breast cancer) for which remission has not been achieved for at least 3 years
• minors
• protected by law (guardianship, curatorship, judicial protection)
• pregnant or breastfeeding
• refusing to participate in the study

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: with LVB infiltration	Drug: LVB infiltration; After general anaesthesia and before the surgical incision; infiltration of 60 ml of levobupivacaine 2.5 mg/ml : 50 ml peritumorally and 10 ml periganglionically
Experimental: infiltration of 60 ml of levobupivacaine 2.5 mg/ml; After general anaesthesia and before the surgical incision; infiltration of 60 ml of levobupivacaine 2.5 mg/ml : 50 ml peritumorally and 10 ml periganglionically	Drug: LVB infiltration; After general anaesthesia and before the surgical incision; infiltration of 60 ml of levobupivacaine 2.5 mg/ml : 50 ml peritumorally and 10 ml periganglionically

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence free survival at 2 years	time between breast surgery and the occurrence of the first recurrence (local, locoregional, or distant) or death from any cause. Patients living without recurrence at the end of follow-up will be censored at the endpoint (24 months after surgery).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival at 2 years	time between breast surgery and death from any cause. Patients living at the end of follow-up will be censored at the endpoint (24 months after surgery).	2 years
Metastasis-free survival at 2 years	time between breast surgery and the first metastasis. Patients without metastasis at the end of follow-up will be censored at the endpoint (24 months after surgery).	2 years
Post-operative pain	Postoperative pain assessed using a Visual Analogue Scale at 30 minutes, 2 hours, 6 hours and 24 hours after breast surgery then at 4 months, 8 months, 12 months, 16 months, 20 months and 24 months after breast surgery	2 years
tolerance to levobupivacaine infiltration	occurrence of adverse effects: cardiac toxicity (arrhythmias, torsades de pointes) and allergy (skin symptoms, tachycardia, low blood pressure)	24 hours

Collaborators and Investigators

• Sponsor: Institut Jean-Godinot

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2032

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: recurrence; Triple-negative breast cancer; levobupivacaine infiltration; surviva
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Skin Diseases; Breast Diseases; Breast Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Recurrence; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 2026_RIPH_02_EPPIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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