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. (TDXdose)

Influence of Patient's Morphological Characteristics on Pharmacokinetic and Toxicity of Trastuzumab-Deruxtecan Administered for Metastatic Breast Cancers

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 Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Breast Cancers
• Intervention / Treatment: Biological: Pharmacokinetics blood samples

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Florence DALENC, MD, Prof; Phone Number: +33531155104; Email: dalenc.florence@iuct-oncopole.fr

Study Locations

• France
  • Angers, France
    • Not yet recruiting
    • Institut de Cancérologie de l'Ouest - Site Angers
    • Contact: Anne Patsouris, MD; Phone Number: +33241352700; Email: anne.patsouris@ico.unicancer.fr
  • Dijon, France
    • Not yet recruiting
    • Centre Georges Francois Leclerc
    • Contact: Sylvain Ladoire, MD,Prof; Phone Number: +33380737506; Email: sladoire@cgfl.fr
  • Lille, France
    • Recruiting
    • Centre Oscar Lambret
    • Contact: Coralie PREBET, MD; Phone Number: +33 320295959; Email: c-prebet@o-lambret.fr
  • Marseille, France
    • Not yet recruiting
    • Institut Paoli Calmettes
    • Contact: Arthur Géraud-Crémieux, MD; Phone Number: +33491223333; Email: geraudcremieuxa@ipc.unicancer.fr
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Contact: Frédéric FITENI, MD; Phone Number: +33466683301; Email: frederic.fiteni@chu-nimes.fr
  • Paris, France
    • Not yet recruiting
    • Institut Curie - Site Paris
    • Contact: Audrey Bellesoeur, MD; Phone Number: +33156245840; Email: audrey.bellesoeur@curie.fr
  • Rennes, France
    • Recruiting
    • Centre Eugene Marquis
    • Contact: Antoine Deleuze, MD; Phone Number: +33299252956; Email: a.deleuze@rennes.unicancer.fr
  • Saint-Herblain, France
    • Not yet recruiting
    • Institut de Cancérologie de l'Ouest - Site Saint Herblain
    • Contact: Julia Quintin, MD; Phone Number: +33240679900; Email: julia.quintin@ico.unicancer.fr
  • Strasbourg, France
    • Recruiting
    • Centre Paul Strauss
    • Contact: Hervé Bischoff, MD; Phone Number: +33368767099; Email: h.bischoff@icans.eu
  • Toulouse, France
    • Recruiting
    • IUCT-O
    • Contact: Florence DALENC, MD, Prof; Phone Number: +33531155104; Email: dalenc.florence@iuct-oncopole.fr
  • Vandœuvre-lès-Nancy, France
    • Not yet recruiting
    • Institut de Cancérologie de Lorraine
    • Contact: Vincent MASSARD, MD; Phone Number: 03 83 59 84 61; Email: v.massard@nancy.unicancer.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Women (or men) aged ≥ 18 years on the day of signing the informed consent with histologically proven breast cancer.
2. Metastatic or locally advanced breast cancer with overexpression/amplification HER2 (IHC +++ or ++ and positive-hybridation in situ) or low HER2 expression (IHC + or ++ and negative-hybridation in situ) and may be ultra-low (in first line, in case of approval).
3. Patient eligible for Trastuzumab-Deruxtecan (T-DXd).
4. Concomitant administration of pertuzumab may be accepted in case of approval in first line for HER2- overexpressed/amplified locally advanced or metastatic breast cancer.
5. Female subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment.

6. Female subjects of childbearing potential must be willing to follow at least one method of contraception or be surgically sterile, or abstain from heterosexual activity for the duration of the study and until 7 months after the last dose of study treatment. Subjects of childbearing potential are those who have not been surgically sterilized and who had menstruation in the last 12 months.

   Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.

7. Male subjects must agree to use at least one method of contraception for the duration of the study and until 4 months after the last dose of study treatment.

   Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.

8. Signed written informed consent.
9. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol.
10. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Peripheral venous access making blood samples difficult.
2. Patients unable to receive T-DXd treatment at a dose of 5.4 mg/kg in cycle 1 (whatever the reason)
3. Patients with known additional malignancy that is progressing or requires active treatment. 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.
4. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
5. Patient pregnant, or breast-feeding.
6. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure.
7. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).
8. Concurrent participation in an experimental drug study.
9. Patient with a known history of hypersensitivity to the active substance of T-DXd or to any of the excipients listed in the SmPC of T-DXd.
10. Patient with severe hepatic impairment defined by TGO and/or TGP > 5 x ULN and Total bilirubin > 1.5 x ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patient with locally advanced or metastatic breast cancer starting T-DXd as standard treatment	Biological: Pharmacokinetics blood samples; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary 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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: toxicities will be assessed using the NCI-CTCAE Version 5.0.		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).	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.	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.	From enrollment to tumor assessment before C9D1 at 6 months of T-DXd treatment (each cycle is 21 days).

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud
• Collaborators: Ligue contre le cancer, France

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: September 11, 2025
• First Submitted That Met QC Criteria: September 19, 2025
• First Posted (Actual): September 26, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Body Mass Index; Trastuzumab-Deruxtecan; Locally or metastatic Breast Cancer; HER2 low-expressed; HER2 over-expressed/amplified
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 25SEIN06

Drug and device information, study documents

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