LifEStyle Intervention to Enhance Efficacy of Neoadjuvant Therapy in Patients With Triple Negative Breast Cancer

NCT06831955 | Recruiting Phase 2

• 1 other identifier: S69524
• Study Type: interventional
• Target: 356
• Locations: 1 country
• Sites: 10

Brief Summary

LESLIE is a multicentric randomized controlled trial in patients with triple negative breast cancer receiving neoadjuvant chemo/immunotherapy (NAT). This trial investigates the hypothesis that adding a cyclic fasting-mimicking diet combined with exercise during the NAT improves the NAT's therapeutic efficacy, treatment tolerability and compliance, as well as improve quality of life.

Conditions

Triple Negative Breast Cancer (TNBC), Early Setting

Keywords

Triple Negative Breast Cancer; Lifestyle Intervention; Neoadjuvant treatment; Fasting-Mimicking Diet; Exercise therapy; Pathological Complete Response

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  pCR, ypT0/Tis ypN0: no invasive residual disease in breast or regional lymph nodes; residual in situ disease allowed

  Surgical specimen (at the time of surgery)

Secondary Outcomes (10)

• Adherence and compliance to FMD

  20 weeks, in case of dose delays up to 30 weeks

• Adherence and compliance to exercise therapy

  20 weeks, in case of dose delays up to 30 weeks

• Adverse Event profile

  Following completion of the NAT, subjects will be followed for 30 days for AEs, SAEs will be collected for 90 days after completion of NAT. An exception is made for heart failure which will be collected till 1 year after NAT.

• Systemic Treatment Completion

  20 weeks, in case of dose delays up to 30 weeks

• Event-Free Survival (EFS) at 3 years

  From the date of randomization to the first documentation of progressive disease or patient death, assessed up to 36 months

Study Arms (2)

Arm A: control arm

ACTIVE COMPARATOR

SOC neoadjuvant therapy is based on the systemic treatment regimen described in the Keynote 522 trial, apart from some minor changes.

Drug: SOC

Arm B: Intervention arm

EXPERIMENTAL

Next to the SOC, the lifestyle intervention (cyclic FMD and exercise) will be part of the treatment.

Other: Exercise Therapy; Dietary Supplement: Fasting-Mimicking Diet; Drug: SOC

Interventions

Exercise Therapy OTHER

The exercise regimen consists of a non-linear aerobic exercise program of 3-4 sessions per week. During days of FMD no exercise will be prescribed.

Arm B: Intervention arm

Fasting-Mimicking Diet DIETARY_SUPPLEMENT

The FMD is a plant-based, low-carbohydrate, low-caloric diet of 4 days , with the fourth day being the day of chemo/immunotherapy. A total of 6 FMD cycles will be administered over the treatment period of 20 weeks.

Arm B: Intervention arm

SOC DRUG

Four cycles of an intravenous infusion of pembrolizumab (200 mg) once every 3 weeks plus paclitaxel (80 mg per square meter of body-surface area once weekly) plus carboplatin (at a dose based on an area under the concentration-time curve of 1.5 mg per milliliter per minute) once weekly in the first 12 weeks, followed by four cycles of epirubicin (90 mg per square meter) plus cyclophosphamide (600 mg per square meter) once every 2 weeks plus pembrolizumab 400mg every 6 weeks or pembrolizumab 200mg every 3 weeks in the subsequent 8 weeks.

Arm A: control arm; Arm B: Intervention arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a biopsy-confirmed diagnosis of stage II-III TNBC
• Patients with tumor stage T1cN1-2, T2N0-N2, T3N0-N2, T4N0-N2
• ER and PR negative is defined as an absent or minimal (≤10%) expression of oestrogen and progesterone receptors and absence of HER2 protein over-expression per ASCO/CAP-guidelines
• All histological subtypes are eligible, including but not limited to invasive breast cancer of no special type (NST) , invasive lobular carcinoma (ILC) etc
• WHO/ECOG performance status of grade 0-1
• The participant is able to perform a CPET test (cardiopulmonary exercise testing)
• Body mass index ≥ 18.5 kg/m²
• Pregnant or breastfeeding women
• Presence of adequate bone marrow and organ function
• HbA1c \<10%

You may not qualify if:

• had a treatment with any of the following:
• any other chemotherapy, immunotherapy or anticancer agents within 5 years of the first dose of study treatment
• injectable hypoglycemics 2. have not have recovered adequately from the toxicity and/or complications from a surgical intervention prior to starting therapy
• prior systemic treatment for breast cancer or other malignancies within 5 years of treatment enrollment, except for adequately treated basal cell or squamous skin cancer or in situ cervical cancer. Other malignancies diagnosed more than 5 years before the diagnosis of breast cancer must have been radically treated without evidence of relapse at the moment of patient enrollment in the trial.
• has a history of an additional malignancy that is progressing or that has required active treatment in the 5 years prior to breast cancer diagnosis. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Prior treatment with anthracyclines
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
• Has any disorder, which in the Investigator's opinion might jeopardize the participant's safety or compliance with the protocol
• Has, as judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
• Active autoimmune diseases requiring systemic treatments
• Patients with type 1 diabetes mellitus
• History of alcohol use disorder (DSM-5)
• History of eating disorder (DSM-5)

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: collaborator
• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator
• AZ Groeninge: collaborator
• Jessa Ziekenhuis Hasselt: collaborator
• UZ Gent, Belgium: collaborator
• UZ Antwerpen: collaborator
• Ziekenhuis ad Stroom, Antwerpen: collaborator
• Institute Gustave Roussy Paris: collaborator

Study Sites (10)

UZ Antwerpen

Antwerp, Belgium

RECRUITING

Ziekenhuis aan de Stroom

Antwerp, Belgium

NOT YET RECRUITING

Cliniques universitaires Saint-Luc (UCLouvain)

Brussels, Belgium

RECRUITING

UZ Brussel

Brussels, Belgium

RECRUITING

UZ Gent

Ghent, Belgium

NOT YET RECRUITING

Jessa Ziekenhuis Hasselt

Hasselt, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium

RECRUITING

University Hospital Leuven

Leuven, Belgium

RECRUITING

Centre Hospitalier Universitaire (CHU) UCL Liège

Liège, Belgium

RECRUITING

Centre Hospitalier Universitaire (CHU) UCL Namur

Namur, Belgium

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Exercise Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• Christine Desmedt, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

• Ann Smeets, MD, PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Desmedt, PhD

CONTACT

+3216321194; christine.desmedt@kuleuven.be

Josephine Van Cauwenbenberge, MD

CONTACT

+3216321194; josephine.vancauwenberge@kuleuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: February 18, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2031
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (10)