Pre and post-menopausal women and men with locally advanced or metastatic HR+/HER2-negative endocrine resistant breast cancer
Conditions
Interventions
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients of both sexes, over 18 years of age with locally advanced or metastatic breast cancer with hormonal receptors and HER2-negative 2. Postmenopausal or Premenopausal Women, 3. No more than one previous line of chemotherapy for locally advanced or metastatic recurrent disease. 4. Disease refractory to CDK4/6 inhibitors. 5. Subtype HER2-E according to the PAM50 analysis confirmed by the designated laboratory. 6. ECOG =1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any TKI directed to ERBB2 (eg, lapatinib, afatinib, dacomitinib, neratinib, tucatinib). 2. Previous treatment with a cumulative dose of epirubicin> 900 mg / m2 or a cumulative dose of doxorubicin> 450 mg / m2. If another anthracycline, or more than one anthracycline, has been used, the cumulative dose should not exceed 450 mg / m2 equivalent of doxorubicin. 3. Uncontrolled heart disease 4. Major chronic digestive disorder with diarrhea as the main symptom 5.Women of childbearing or pregnant age 6. Pleural effusion, pericardial effusion 7. Uncontrolled hypercalcemia 8. * Additional malignant neoplasm confirmed to be in progression or have needed active treatment in the last 3 years. 9. Presence of active metastases in the CNS or carcinomatous meningitis. 10. * History of pneumonitis (non-infectious) that has required steroids or active pneumonitis. 11. * Previous solid organ transplant 12. Presence of an active infection that requires systemic treatment. 13. * Known history of human immunodeficiency virus (HIV) infection. 14. * Known history of hepatitis B virus infection or known active hepatitis C virus infection 15. Inability or unwillingness to swallow tablets. 16. Known hypersensitivity to any of the components of the product under investigation, the need for combined treatment or loperamide. 17. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A4/P-gp isoform of cytochrome P450 within 5 days prior to inclusion. 18. * Presence of a psychiatric or substance abuse disorder 19. Being pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy in terms of Progression-Free Survival at 6 months (PFS6) of neratinib in combination with endocrine therapy in HR+/HER2- HER2-E subtype advanced breast cancer defined by the PAM50 assay.;Secondary Objective: 1.To determine the clinical benefit of neratinib in combination with endocrine therapy in terms of: 1.1.Clinical Benefit Rate at 6 months (CBR6) determined locally by the investigator according to RECIST v1.1. 1.2.Overall response rate (ORR) determined locally by the investigator according to RECIST v1.1. 1.3.Progression free survival (PFS), as determined locally by the investigator according to RECIST v.1.1, or death from any cause, whichever occurs first. 1.4 Duration of response (DOR) determined locally by the investigator according to RECIST v1.1.. 1.5 Time to response (TtR) defined as the time from first treatment administration to the first objective tumor response (tumor shrinkage of >=30%) observed for patients who achieved a CR or PR 1.6 PFS on study treatment compared to PFS on prior line of therapy (pre-PFS) 2 To evaluate the safety and tolerability of neratinib + letrozole;Primary end point(s): Progression-Free Survival at 6 months (PFS6) defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria).;Timepoint(s) of evaluation of this end point: at 24 weeks after first treatment administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Clinical Benefit Rate at 6 months (CBR6) defined as a Complete response (CR), Partial response (PR) or Stable Disease (SD) for at least 24 weeks, as determined locally by the investigator according to RECIST v1.1. 2. Overall Response rate (ORR) as determined locally by the investigator according to RECIST v1.1 3.Progression free survival (PFS) defined as the time from first treatment administration to the first occurrence of disease progression, as determined locally by the investigator according to RECIST v.1.1, or death from any cause, whichever occurs first. 4.Duration of response (DoR) defined as the time from the first occurrence of a documented objective response to disease progression, as determined locally by the investigator through use of RECIST v.1.1, or death from any cause, whichever occurs first. 5.Time to response (TtR) defined as the time from first treatment administration to the first objective tumor response (tumor shrinkage of =30%) observed for patients who achieved a CR or PR. 6.PFS on study treatment compared to PFS on prior line of therapy (pre-PFS). 7. Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, including dose reductions, delays and treatment discontinuations.;Timepoint(s) of evaluation of this end point: -6 month for CBR6 -Rest of secondary objective will be mesure upon lost of follow up | — |
Countries
Portugal, Spain
Contacts
Public ContactAREA INVESTIGACION CLINICA
SOLTI
Outcome results
None listed