Triple Negative Breast Cancer (TNBC), Early SettingPhase 2LESLIENCT06831955
LifEStyle Intervention to Enhance Efficacy of Neoadjuvant Therapy in Patients With Triple Negative Breast Cancer
A Phase 2 study testing Exercise Therapy, Fasting-Mimicking Diet and SOC in people with Triple Negative Breast Cancer (TNBC), Early Setting, run by Universitaire Ziekenhuizen KU Leuven at 10 sites in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer (TNBC), Early Setting
- What is being tested?
- Exercise Therapy, Fasting-Mimicking Diet and SOC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 356 participants
- Where
- 10 sitesBelgium
- Study dates
- 1 Feb 2026to 1 Sep 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- Body mass index ≥ 18.5 kg/m²
- Pregnant or breastfeeding women
- Presence of adequate bone marrow and organ function
- HbA1c <10%
Who cannot join
- 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
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- 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)
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Belgium10 sites, 10 recruiting
- Recruiting
UZ Antwerpen
Antwerp
Sevilay Altintas, MD, PhD, +3238213000, sevilay.altintas@uza.be
Sevilay Altintas, MD, PhD
- Not yet recruiting
Ziekenhuis aan de Stroom
Antwerp
Kevin Punie, MD, +3234433737, kevin.punie@gza.be
Kevin Punie, MD
- Recruiting
Cliniques universitaires Saint-Luc (UCLouvain)
Brussels
Francois Duhoux, francois.duhoux@saintluc.uclouvain.be
Francois Duhoux, MD, PhD
- Recruiting
UZ Brussel
Brussels
Christel Fontaine, MD, PhD, +3224774111, christel.fontaine@uzbrussel.be
Christel Fontaine, MD, PhD
- Not yet recruiting
UZ Gent
Ghent
Eline Naert, MD, PhD, +3293322111, eline.naert@uzgent.be
Eline Naert, MD, PhD
- Recruiting
Jessa Ziekenhuis Hasselt
Hasselt
Jeroen Mebis, MD, PhD, +3211335511, jeroen.mebis@jessazh.be
Jeroen Mebis, MD, PhD
- Recruiting
AZ Groeninge
Kortrijk
Marianne Hanssens, MD, +3256636363, marianne.hanssens@azgroeninge.be
Marianne Hanssens, MD
- Recruiting
University Hospital Leuven
Leuven
Ann Smeets, MD, PhD, 016332211, ann.smeets@uzleuven.be
Ann Smeets, MD, PhD
- Recruiting
Centre Hospitalier Universitaire (CHU) UCL Liège
Liège
Pierre Foidart, pierre.foidart@chuliege.be
Pierre Foidart, MD, PhD
- Recruiting
Centre Hospitalier Universitaire (CHU) UCL Namur
Namur
Donatienne Taylor, MD, donatienne.taylor@chuuclnamur.uclouvain.be
Donatienne Taylor, MD
About this study
Official title: The LESLIE Trial: LifEStyle Intervention to Enhance Efficacy of Neoadjuvant Systemic Therapy in Patients With Triple Negative Breast Cancer
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.
Read the detailed description
Leslie is a 2-arms randomized (2:1) Phase IIb clinical trial including 356 patients that will investigate whether combining a cyclic FMD-based intervention with exercise concomitant with neoadjuvant systemic therapy may have a beneficial effect on treatment response, survival, treatment tolerability and compliance, as well as quality of life of patients with TNBC. The neoadjuvant treatment will last for 21 weeks in both arms. Visits to the day clinic will be scheduled for administration of Standard of Care (SOC) in combination with 2-weekly visits to physiotherapists and online support of onco-dietician for patients from arm B.
The control group (arm A): SOC neoadjuvant therapy is based on the systemic treatment regimen described in the Keynote 522 trial, apart from some minor changes. It consists of 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. All treatments after surgery will be administered according to the institutional guidelines.
The interventional group (arm B): Next to the SOC, the lifestyle intervention (cyclic FMD and exercise) will be part of the treatment. 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. 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.
- Being tested
- Exercise Therapy, Fasting-Mimicking Diet, SOC
- Keywords
- Triple Negative Breast Cancer, Lifestyle Intervention, Neoadjuvant treatment, Fasting-Mimicking Diet, Exercise therapy, Pathological Complete Response
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise TherapyOther
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.
Fasting-Mimicking DietDietary 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.
SOCDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: SOC |
| Arm B: Intervention arm | Experimental | Next to the SOC, the lifestyle intervention (cyclic FMD and exercise) will be part of the treatment. Receives: Other: Exercise Therapy; Dietary Supplement: Fasting-Mimicking Diet; Drug: SOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR)
pCR, ypT0/Tis ypN0: no invasive residual disease in breast or regional lymph nodes; residual in situ disease allowed
Measured: Surgical specimen (at the time of surgery)
Secondary outcomes (10)
Adherence and compliance to FMD
Adherence is defined as the ratio of how many days the patient complies to the FMD (without 2 minor or 1 major deviation), divided by the in total 24 planned days of FMD. Compliance will be measured at the end of each FMD cycle based on the incidence of minor and major deviations from the prescribed dietary regimen.
Measured: 20 weeks, in case of dose delays up to 30 weeks
Adherence and compliance to exercise therapy
Exercise attendance is calculated as the number of training sessions attended divided by the total 75 planned sessions. Compliance is calculated based on the relative dose intensity (RDI). Relative dose intensity (RDI) is defined as the ratio of total completed to total planned cumulative dose, expressed as a percentage.
Measured: 20 weeks, in case of dose delays up to 30 weeks
Adverse Event profile
The type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), seriousness, time till onset and duration of Adverse Events (AEs)/SAEs, immune-related AEs and any laboratory abnormalities
Measured: 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
RDI is defined as the amount of drug administered per unit of time (=delivered total dose in mg/m2 divided by actual time used to complete treatment in a number of weeks) as a fraction of the standard amount of drug per unit of time (=standard total dose in mg/m2 divided by standard time to complete treatment in a number of weeks)
Measured: 20 weeks, in case of dose delays up to 30 weeks
Event-Free Survival (EFS) at 3 years
at 3 years is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause. Patients without documented event at the time of the analysis will be censored at the date of the last follow-up
Measured: From the date of randomization to the first documentation of progressive disease or patient death, assessed up to 36 months
Distant Metastasis-Free Survival at 3 years
is defined as the time from randomization to the occurrence of distant metastasis or death. Patients without documented event at the time of the analysis will be censored at the date of the last follow-up.
Measured: From surgery to the occurrence of distant metastases or patient death, assessed up to 36 months
Residual Cancer Burden
Residual Cancer Burden (RCB) continuous score and categories calculated using the classification by Symmans et al with RCB-0 (pCR [ypT0/Tis ypN0]), RCB-I (minimal residual disease), RCB-II (moderate residual disease), and RCB-III (extensive residual disease or progression on neoadjuvant therapy). In the breast the primary tumor beds' dimensions and overall cancer cellularity is considered, including the percentage of cancer that is in situ disease in tumor bed. For lymph nodes the number of positive lymph nodes and the size of the largest metastatic deposit is used.
Measured: Surgical specimen (at the time of surgery)
Quality of life (QoL)
Quality of life (QoL): as assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTCQLQ- BR42. The questionnaires will be filled in at baseline, at C8 and C14, week before surgery and at 3 months, 6 months, 1 year, 2 years and 3 years postoperative.
Measured: From the date of randomization up to 36 months
Body Composition
as evaluated with weekly bioimpedance measurements (fat-free mass, fat mass, phase angle, extracellular mass-to-body cell mass ratio (ECM/BCM), total body water and intracellular water). This scale is designed following the ISO 13 485 and the Medical Device Regulation (MDR) guidelines. After com
Measured: From the date of randomization up to 36 months
Fatigue
Fatigue: as assessed using the FACIT-Fatigue v4.0 questionnaire. The questionnaire will be filled in at baseline, at C8 and C14, week before surgery and at 3 months, 6 months, 1 year, 2 years and 3 years postoperative.
Measured: From the date of randomization up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start1 Feb 2026
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast Cancer (TNBC), Early SettingStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 356 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, AZ Groeninge, Jessa Hospital, University Hospital, Ghent, UZ Antwerpen, Ziekenhuis ad Stroom, Antwerpen, Universitair Ziekenhuis Brussel, Centre Hospitalier Universitaire UCLouvain Namur, Centre Hospitalier Universitaire de Liege, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Responsible party
- Sponsor
- Investigators
- Christine Desmedt, PhD, Principal investigator, KU LeuvenAnn Smeets, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06831955
- Sponsor's protocol ID
- S69524
- Acronym
- LESLIE
- Status last verified
- Mar 2026
- First submitted
- 5 Dec 2024
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No