DOSABEMA-Pharmacokinetic model of abemaciclib: correlation with severe diarrhea as the primary toxicity endpoint in patients with hormone receptor-positive localized breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Poitiers

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-01-06

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU de Poitiers · PHRNC-DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

To determine the relationship between the probability of occurrence of a serious diarrhoeal adverse event (grade 2 and +) and plasma exposure to abemaciclib and its metabolites (M2 and M20), in patients with HR+, HER2- breast cancer at high risk of recurrence receiving adjuvant abemaciclib.

Secondary objectives 3

1. To determine the relationship between the probability of occurrence of a serious neutropenic adverse event (grade 3 and 4) and plasma exposure to abemaciclib and its metabolites (M2 and M20), in patients with HR+, HER2- breast cancer at high risk of recurrence receiving adjuvant abemaciclib.
2. To determine the relationship between the probability of occurrence of a serious neutropenic adverse event (grade 3 and 4) and plasma exposure to abemaciclib and its metabolites (M2 and M20), in patients with HR+, HER2- breast cancer at high risk of recurrence receiving adjuvant abemaciclib.
3. To assess the free fraction (fu) of abemaciclib concentrations at different treatment protocol times in the target population. (Only at Poitiers University Hospital)

Conditions and MedDRA coding

HR+, HER2- breast cancer at high risk of recurrence

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Women aged ≥ 18 with breast cancer of any histology
2. Type Luminous A or B with positive hormone receptors (>10% expression for oestrogen receptor and/or progesterone receptor) and negative or low HER2 epidermal growth factor receptor (as defined by GEFPICS1)
3. Stage 2 or stage 3 according to the international classification, translated into the SENORIF recommendation
4. Who have undergone complete excision surgery (R0 on the invasive tumour and/or on the ductal entity in situ) after neoadjuvant or non-neoadjuvant chemotherapy;
5. Defined as being at high risk of recurrence according to the Monarch-E study, at the initial diagnosis of the disease: either ≥ 4 axillary nodes involved (involvement ≥N2), or 1-3 axillary nodes involved (involvement ≥N1) associated with an Elston Ellis grade 3 or a tumour ≥ 5 cm
6. Initiation of adjuvant abemaciclib therapy combined with hormone therapy
7. Patient ECOG performans status between 0 ≤2
8. Patient with a PNN count defined as normal prior to the first dose of abemaciclib, i.e. an absolute PNN count ≥ 1500/mm3 (≥ 1.5 x 109/L) without GCSF injection within 15 days prior to the biological work-up, as well as a platelet count ≥ 100 000/mm3 and a haemoglobin level ≥ 8g/dL.
9. Patient with the psychological and mental capacity to understand the protocol and sign the consent form alone
10. Must be affiliated to the social security system or benefit from it through a third party
11. Have signed the consent form for the study after reading the information note

Exclusion criteria 8

1. Previous treatment with an anti-CDK4/6 (palbociclib, ribociclib, abemaciclib) for any indication.
2. History of invasive cancer of any histology in the last 2 years, with the exception of superficial skin tumours, not considered to be in complete remission.
3. Presence of functional or inflammatory colorectal disease (Crohn's disease, ulcerative colitis) causing chronic diarrhoea (as defined by the WHO as at least 3 bowel movements per day and/or liquid stools for at least 1 month).
4. Patients who have undergone total gastrectomy or suffer from short bowel syndrome
5. Patients unable to sign the consent form for social reasons (illiteracy) or physical reasons (central nervous system disease).
6. Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by judicial or administrative decision, persons staying in a health or social care institution, adults under legal protection and, finally, patients in emergency situations.
7. Pregnant or breastfeeding women, women of childbearing age who are not using highly effective contraception (e.g., double-barrier contraception) during treatment and for at least 3 weeks after stopping treatment (The duration of contraception required for concomitant treatments, if any, should also be taken into account.)
8. Hypersensitivity to any of the excipients listed in section 6.1 of the abemaciclib (Verzenios) summary of product characteristics.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The probability of severe diarrhoea (grades 2, 3 and 4 according to CTCAE v5.0) occurring as a result of exposure to abemaciclib and its metabolites will be characterised by a mixed-effects joint model, combining longitudinal, pharmacokinetic (continuous) and toxicity (survival) data.

Secondary endpoints 3

1. The probability of severe neutropenia (grades 3 and 4 according to the current CTCAE) occurring as a result of exposure to abemaciclib and its metabolites will be characterised by a mixed-effects joint model, combining longitudinal pharmacokinetic data pharmacokinetic (continuous type) and pharmacodynamic (neutrophil concentration, continuous type) data.
2. Validation of the mixed-effects PK/PD model using standard diagnostic tools (diagnostic plots of data fit, visual predictive checks, estimation precision, shrinkage).
3. The ‘fu’ of abemaciclib concentrations will be modelled within the mixed-effects PK/PD model, and any correlation with clinical and biological covariates will be evaluated.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

Sponsor organisation

Centre Hospitalier Universitaire De Poitiers

Address

2 Rue De La Miletrie

City

Poitiers

Postcode

86000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Coordination investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Coordination investigator

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

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

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