This is a multicenter, prospective, non-randomized, open-label, pharmacokinetic study, aiming to compare the plasma exposure of the payload (free-DXd) in patients treated by T-DXd for locally advanced or metastatic breast cancer according to their BMI. The primary objective is to compare plasma exposition of the payload (free-DXd) between overweight or obese (BMI\>25) and normal weight (BMI≤25) breast cancer patients during the first 3 cycles of Trastuzumab-Deruxtecan (T-DXd). A total of 210 patients will have to be enrolled in this study with the following repartition: N = 105 patients with a BMI ≤ 25 (normal weight patients). N = 105 patients with a BMI \> 25 (overweight or obese patients) with at least 30 obese patients (BMI\>30).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
210
Blood samples will be collected at different time points during the first four treatment cycles and at the end of T-DXd treatment or at 24 months after inclusion in case of T-DXd continuation beyond this time period.
Institut de Cancérologie de l'Ouest - Site Angers
Angers, France
NOT_YET_RECRUITINGCentre Georges François Leclerc
Dijon, France
NOT_YET_RECRUITINGCentre Oscar Lambret
Lille, France
NOT_YET_RECRUITINGInstitut Paoli Calmettes
Marseille, France
NOT_YET_RECRUITINGCHU de Nîmes
Nîmes, France
NOT_YET_RECRUITINGInstitut Curie - Site Paris
Paris, France
NOT_YET_RECRUITINGCentre Eugène Marquis
Rennes, France
NOT_YET_RECRUITINGInstitut de Cancérologie de l'Ouest - Site Saint Herblain
Saint-Herblain, France
NOT_YET_RECRUITINGCentre Paul Strauss
Strasbourg, France
RECRUITINGIUCT-O
Toulouse, France
RECRUITINGPrimary Outcome Measure
Plasma exposure of free-DXd (payload) will be measured by the cumulative AUC (Area under the concentration vs. time curve) over the first 3 cycles or until an event (interruption or dose concession for toxicity) divided by the number of corresponding cycles. These AUCs will be determined by Bayesian estimation (Posthoc values) using a non-linear mixed-effects approach.
Time frame: From the 1st cycle of T-DXd (C1D1) to the end of the 3rd cycle of T-DXD (each cycle is 21 days) treatment or until an event (interruption or dose concession for toxicity) if it occurs before the 3rd cycle.
Safety: toxicities will be assessed using the NCI-CTCAE Version 5.0.
Time frame: From enrollment to the end of patient participation up to 24 months after inclusion
Efficacy: Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time from inclusion until progression or death; patients alive and without documented progression at last follow-up news are censored at this date or at initiation of new anticancer treatment (if applicable).
Time frame: From inclusion until progression or death up to 24 months after inclusion
Secondary pharmacokinetic criteria
A population PK model will be performed to quantify the impact of several patient characteristics: morphological data (weight, height, BMI, lean mass, etc.), biological data (inflammation markers, albuminemia, liver enzymes, etc.), demographic data (age), on the PK parameters (elimination clearance, volume of distribution) of T-DXd and free-DXd.
Time frame: From C1D1 to definitive stop of T-DXd treatment up to 24 months after inclusion
Body composition parameters
Skeletal muscle mass index or density and lean body mass before treatment initiation and during the active treatment phase (at 3 months tumor assessment before C5D1 and at 6 months; tumor assessment before C9D1) using the "Cassandra" algorithm.
Time frame: From enrollment to tumor assessment before C9D1 at 6 months of T-DXd treatment (each cycle is 21 days).
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