everolimus for Metastatic breast cancer | Estrogen receptor-positive breast cancer | HER2-negative breast cancer

Inclusion criteria

• {"criterion_text":"- patient over 18 years of age"}
• {"criterion_text":"- histologically proven estrogen receptor positive and HER2 receptor negative invasive breast tumour"}
• {"criterion_text":"- Irresectable or metastatic disease"}
• {"criterion_text":"- satisfactory overall performance status: ECOG 0-1"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- at least one previous line of endocrine-based palliative therapy that included a CDK4/6 inhibitor."}
• {"criterion_text":"- previous palliative chemotherapy is allowed."}
• {"criterion_text":"- Postmenopausal female patient, or if premenopausal female or male patient, simultaneous use of GNRH analogue"}

Exclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Pregnancy or if the patient does not agree to use an appropriate non-hormonal method of contraception."}
• {"criterion_text":"- known allergy or hypersensitivity to everolimus, exemestane or their components"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured with the FACT-B quality of life test (FACT-B total score). Comparison of the average FACT-B total score between the two arms at the end of four-month treatment; hypothesis of 20% improvement in divided-dose arm versus single-dose arm."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30 domains (global health, physical functioning, fatigue) and EORTC QLQ-BR23 systemic treatment side effect; change in average scores by end of four-month treatment (>=10 points considered)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Objective response rate per RECIST v1.1 (complete or partial remission). Non-responders include those without such responses or with unevaluable efficacy."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v5.0; safety population includes all patients receiving at least one dose of everolimus."}
• {"endpoint_text":"- Evolution of pharmacokinetic values (Ctrough and Cmax) in the two arms","definition_or_measurement_approach":"Pharmacokinetic assessment of Ctrough and Cmax values in each arm over time."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients with dose escalation based on PK parameters (Ctrough and Cmax) who tolerate and maintain increased dose (possible increases to 12.5 mg/day or 15 mg/day) until study end; hypothesis ~20%."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Relative dose intensity calculated as taken dose divided by planned dose for each patient; analysis includes all patients receiving at least one dose."}

Hungary

Earliest CTIS Part Ii Submission Date

28-01-2025

Latest Decision Or Authorization Date

19-03-2025

Processing Time Days

50

Number Of Sites

1

Number Of Participants

64

Primary sponsor

Full Name

Orszagos Onkologiai Intezet

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Hungary