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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
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.
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.
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.
UZ Antwerpen
Antwerp, Belgium
RECRUITINGZiekenhuis aan de Stroom
Antwerp, Belgium
NOT_YET_RECRUITINGCliniques universitaires Saint-Luc (UCLouvain)
Brussels, Belgium
Pathological Complete Response (pCR)
pCR, ypT0/Tis ypN0: no invasive residual disease in breast or regional lymph nodes; residual in situ disease allowed
Time frame: Surgical specimen (at the time of surgery)
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.
Time frame: 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.
Time frame: 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
Time frame: 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)
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TREATMENT
Masking
NONE
Enrollment
356
UZ Brussel
Brussels, Belgium
RECRUITINGUZ Gent
Ghent, Belgium
NOT_YET_RECRUITINGJessa Ziekenhuis Hasselt
Hasselt, Belgium
RECRUITINGAZ Groeninge
Kortrijk, Belgium
RECRUITINGUniversity Hospital Leuven
Leuven, Belgium
RECRUITINGCentre Hospitalier Universitaire (CHU) UCL Liège
Liège, Belgium
RECRUITINGCentre Hospitalier Universitaire (CHU) UCL Namur
Namur, Belgium
RECRUITINGTime frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: From the date of randomization up to 36 months