Influence des caractéristiques morphologiques sur la pharmacocinétique et la toxicité du trastuzumab-déruxtécan chez des patients ayant un cancer du sein métastatique (TDXdose)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncopole Claudius Regaud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Oct 2025 → ongoing

Decision date (initial)

2025-10-08

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ligue nationale Contre le Cancer

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

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).

Secondary objectives 5

1. - To compare the frequency and the intensity of the adverse effects (AE) between the two groups (i.e. overweight or obese patients vs. normal weight patients)
2. - To evaluate the relationship between pharmacokinetic (plasma concentration or exposition of T-DXd or free-DXd) and toxicity of T-Dxd (AE).
3. - To evaluate the relationship between pharmacokinetic (plasma concentration or exposition of T-DXd or free-DXd) and efficacy of treatment (PFS).
4. - To develop a population pharmacokinetic model of T-DXd and evaluate the impact of different covariates (morphologic including alternatives body composition parameters, demographic, biological) on pharmacokinetic parameters.
5. - To evaluate the link between sarcopenia (initial status and its evolution during treatment) and the effects of T-DXd (AE and efficacy).

Conditions and MedDRA coding

Metastatic breast cancers

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Women (or men) aged ≥ 18 years on the day of signing the informed consent with histologically proven breast cancer.
2. 2. Metastatic or locally advanced breast cancer with overerexpression/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. 3. Patient eligible for Trastuzumab-Deruxtecan (T-DXd).
4. 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. 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. 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. 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. 8. Signed written informed consent.
9. 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. 10. Patient affiliated to a Social Health Insurance in France.

Exclusion criteria 10

1. 1. Peripheral venous access making blood samples difficult.
2. 2. Patient unable to receive T-DXd treatment at a dose of 5.4 mg/kg in cycle 1 (whatever the reason).
3. 3. Patient 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. 4. Patient with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
5. 5. Patient pregnant, or breast-feeding.
6. 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. 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. 8. Concurrent participation in an experimental drug study.
9. 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. 10. Patient with severe hepatic impairment defined by TGO and/or TGP > 5 x ULN and Total bilirubin > 1.5 x ULN.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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. Differences between the two groups will be assessed using Student’s test (or Mann Whitney if applicable).

Secondary endpoints 4

1. • Safety: Safety will be assessed through recording of adverse events using NCI-CTCAE toxicity classification v5.0. AEs will be summarized by descriptive statistics and differences between groups will be assessed using Chi-squared or Fisher’s exact test.
2. • Efficacy: The Kaplan-Meier approach will be used to estimate PFS rates for each group. To consider immortal time bias, the association between plasma exposure (or plasma concentration) and PFS will be assessed using a Cox proportional hazards model with time-dependent variable. Cox model will be adjusted on clinico-pathological variables of interest. A complementary analysis will be conducted using Landmark approach at different time points.
3. • Association between Progression Free Survival and body composition will be assessed using a similar approach to the one used for association with plasma exposure.
4. • Association between plasma exposure and safety will be assessed using logistic regression models. The ORs and corresponding confidence intervals (CIs) will be reported.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncopole Claudius Regaud

Sponsor organisation

Oncopole Claudius Regaud

Address

1 Avenue Irene Joliot Curie

City

Toulouse

Postcode

31100

Country

France

Scientific contact point

Organisation

Oncopole Claudius Regaud

Contact name

Pr. Florence DALENC

Public contact point

Organisation

Oncopole Claudius Regaud

Contact name

Muriel MOUNIER

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications