Individualized everolimus therapy in metastatic breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Orszagos Onkologiai Intezet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-03-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

National Institute of Oncology, Hungary

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

Change in the quality of life in the two study arms, examined with the FACT-B quality of life test

Secondary objectives 1

1. To determine whether split-daily (everolimus) treatment is preferable to single daily dosing in terms of quality of life (multiple measures), efficacy, side effects and pharmacokinetics.

Conditions and MedDRA coding

metastatic breast cancer

Regulatory references

Plan to share IPD

No

IPD plan description

We don't plan to share individual patient data with third parties. The data evaluation and statistical analysis will take place on the site using anonymized data.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. patient over 18 years of age
2. histologically proven estrogen receptor positive and HER2 receptor negative invasive breast tumour
3. Irresectable or metastatic disease
4. satisfactory overall performance status: ECOG 0-1
5. adequate organ function a. Neutrophil count ≥ 1.5 G/l, platelet count ≥ 100 G/l, haemoglobin ≥ 10 g/dl b. GOT/GPT less than 2.5 times the upper limit of the normal range (5 times in case of liver metastasis) c. bilirubin less than 1,5 times the upper limit of the normal range (except Gilbert's disease where less than 3 times) d. creatinine less than 1,5 times the upper limit of the normal range or eGFR higher than 60 ml/min
6. at least one previous line of endocrine-based palliative therapy that included a CDK4/6 inhibitor.
7. previous palliative chemotherapy is allowed.
8. Postmenopausal female patient, or if premenopausal female or male patient, simultaneous use of GNRH analogue

Exclusion criteria 4

1. Known significant cardiac disease: major arrhythmia or significant conduction disturbance (grade 2 or more in severity), infarction or unstable angina within 6 months, collapse of cardiac origin without appropriate therapy, long QT syndrome, heart failure
2. any other serious acute or chronic condition (organic or psychiatric disease, laboratory abnormality, severe pulmonary disease) which, in the opinion of the treating physician, would result in an unacceptable increase in the risk of therapy
3. Pregnancy or if the patient does not agree to use an appropriate non-hormonal method of contraception.
4. known allergy or hypersensitivity to everolimus, exemestane or their components

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the quality of life in the two study arms, examined with the FACT-B quality of life test. Hypothesis: the difference between the averages of the quality of life measured on the basis of the FACT-B questionnaire (FACT-B total score) between the two arms (FACT-BA-arm-FACT-BB-arm) improves by 20% in the divided-dose arm in favor of the sinle-dose arm at the end of the four-month treatment.

Secondary endpoints 6

1. Examination of quality of life in the two arms: does the difference in the average of the quality of life values measured with each test between the two arms change by at least 10 points by the end of the four-month treatment, measured with the following specific tools o EORTC C30 global health value o EORTC C30 physical functionality o EORTC C30 fatigue o EORTC BR23 systemic treatment side effect
2. The ratio of the response rate in the two arms. Clinical response is defined as complete or partial remission according to RECIST v1.1. Patients who do not develop such a response, or for whom efficacy cannot be assessed for any reason, are considered non-responders.
3. Safety study: occurrence and severity of side effects in the two arms evaluated according to NCI CTCAE v5.0. All patients who received at least one dose of everolimus are included in the analysis.
4. Evolution of pharmacokinetic values (Ctrough and Cmax) in the two arms
5. Rate of successful dose increase based on pharmacological data: determining whether it is possible to increase the dose and maintain the increased dose based on the pharmacological parameters. If a dose increase is justified based on the serum levels (Ctrough and Cmax) according to the protocol, will the patient tolerate the increased dose (12.5 mg/day or 15 mg/day) until the end of the study. Hypothesis: 20% of patients have the possibility of a successful dose increase.
6. Dose intensity: evaluation of the relative dose intensity (taken dose/planned dose) in the two arms. All patients who received at least one dose of everolimus are included in the analysis.

Investigational products

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

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Orszagos Onkologiai Intezet

Sponsor organisation

Orszagos Onkologiai Intezet

Address

Rath Gyorgy Utca 7-9, Kerulet Kerulet

City

Budapest XII

Postcode

1122

Country

Hungary

Scientific contact point

Organisation

Orszagos Onkologiai Intezet

Contact name

Gabor Rubovszky

Public contact point

Organisation

Orszagos Onkologiai Intezet

Contact name

Gabor Rubovszky

Locations

1 EU/EEA country · 1 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 8 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