Prevention of Ribociclib-related hepatotoxicity in breast cancer patients: a phase II, multicentre, open label, single arm trial of Silimarin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Oncotech Impresa Sociale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2026-02-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Elleva Pharma srl

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy

To demonstrate a reduction of Grade ≥2 AST/ALT increase in the first 6-months of Ribociclib + ET using Silimarin 200 mg.

Secondary objectives 7

1. To observe the reduction in percentage of All Grade AST/ALT increase.
2. To observe the reduction in percentage of Grade 3 or Grade 4 AST/ALT increase.
3. To observe a reduction in time to resolution of Grade≥ 2 AST/ALT events.
4. To observe a delay in the onset of Grade≥ 2 AST/ALT increase.
5. To observe the dose intensity of Ribociclib + ET.
6. To observe permanent discontinuations, dose interruptions and dose adjustments during the 6 months period from the beginning of the treatment.
7. To describe differences in the management of hepatotoxicity and correlate the different strategies to time to resolution of the adverse event

Conditions and MedDRA coding

hormone receptor positive, HER2-negative breast cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men or women aged 18 years or older.
2. Histologically and/or cytologically confirmed diagnosis of hormone receptor positive, HER2-negative breast cancer.
3. Candidated to Ribociclib + endocrine therapy as per local guidelines.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0–2.
5. Adequate liver function at baseline [alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be < ULN.]
6. Patients must be able to communicate with the investigator and comply with the requirements of the study procedures.

Exclusion criteria 7

1. Patients who have not had resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤1 (except other toxicities not considered a safety risk for the patient at investigator's discretion).
2. Patients are concurrently using other anti-cancer therapy, different from Ribociclib + endocrine therapy.
3. Patients have any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol.
4. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels ≥ ULN, and acute or chronic hepatopathies.
5. Contraindication to ribociclib as per drug SMPC
6. Contraindication to Silimarin 200 mg as per drug SMPC: Hypersensitivity to the active ingredient or to any of the excipients listed; Hypersensitivity to plants of the Asteraceae (Compositae) family; Conditions of mechanical obstruction of the biliary ducts.
7. Concomitant use of CYP3A4 inducers/inhibitors

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The incidence rate of Grade ≥ 2 AST/ALT increase from the beginning of the treatment to 6 months

Secondary endpoints 6

1. The incidence rate of all grade AST/ALT increases, from the beginning of the treatment to 6 months after, compared to historical controls from phase III trials
2. Time to resolution of grade ≥ 2 AST/ALT increase to grade 1 or below: comparison with historical controls from phase III trials.
3. Time to onset of grade ≥ 2 AST/ALT increase: comparison with historical controls from phase III trials.
4. Dose intensity of Ribociclib + ET throughout the 6 months.
5. Cumulative percentage of permanent discontinuations, dose interruptions and dose adjustments during the 6 months period from the beginning of the treatment.
6. To describe differences in the management of hepatotoxicity and correlate the different strategies to time to resolution of the adverse event

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Oncotech Impresa Sociale

Sponsor organisation

Fondazione Oncotech Impresa Sociale

Address

Piazza Luigi Di Savoia 22

City

Milan

Postcode

20124

Country

Italy

Scientific contact point

Organisation

Fondazione Oncotech Impresa Sociale

Contact name

Michelino De Laurentiis

Public contact point

Organisation

Fondazione Oncotech Impresa Sociale

Contact name

Michelino De Laurentiis

Third parties 1

Locations

1 EU/EEA country · 17 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 11 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