HER2+, HR+ Early stage Breast Cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: PT Classification code 10083234 Term: Hormone receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Nerlynx
Product Name: Neratinib
Product Code: [PB-272
HKI-272]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: neratinib
CAS Number: 698387-09-6
Current Sponsor code: Neratinib
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient > or = 18 years of age at signing of informed consent. 2. Histologically confirmed Stage IB through Stage IIIC primary adenocarcinoma of the breast according to the 8th edition of the TNM Classification of Breast Cancer, by the UICC (Union for International Cancer Control). 3. Documented HER2-positive disease based on local laboratory determination according to ASCO/CAP 2018 criteria. 4. Documented hormone receptor-positive (HR+) disease, defined as oestrogen receptor (ER) and/or progesterone receptor (PR) > or = 1% based on local laboratory determination. 5. Patients must have completed prior neoadjuvant/adjuvant trastuzumab-based therapy (eg, trastuzumab-based treatments including trastuzumab-emtansine [T-DM1]) or experienced side effects that resulted in early discontinuation of trastuzumab-based therapy that have since resolved (pertuzumab therapy is accepted but not mandatory). 6. The last dose of trastuzumab-based therapy must have been given to the patient >2 weeks and =1 year (365 days) before first dose of neratinib. 7. Left ventricular ejection fraction (LVEF) > or = 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO). 8. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. 9. Negative ß-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. [Women are considered postmenopausal if they are > or = 12 months without menses, in the absence of endocrine or anti-endocrine therapies]. 10. Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized male partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 30 days after the last dose of the medicinal products. Male patient with female partner of childbearing potential must agree and commit with this female partner to use a highly effective method of contraception (ie, any of the above methods, or for females, hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of medicinal products. 11. Recovery (ie, to Grade 1 or baseline) from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia, neuropathy, and nail changes). 12. Provide written, informed consent to participate in the study and follow the study procedures. 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 315 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 315
Exclusion criteria
Exclusion criteria: 1. Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry. 2. Currently receiving chemotherapy, radiation therapy, immunotherapy, or biological therapy for breast cancer (adjuvant endocrine therapy is allowed). 3. Major surgery within or = 2), unstable angina, myocardial infarction within 12 months of enrolment, or ventricular arrhythmia. 5. QTc interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP). 6. Screening laboratory assessments outside the following limits: Laboratory Parameters: Required Limit for Exclusion Absolute neutrophil count (ANC): 1.5 x institutional upper limit of normal (ULN) (in case of known Gilbert’s syndrome, 2.5 x institutional ULN. Creatinine: Creatinine clearance or = 2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] diarrhoea of any etiology at baseline); or gastroparesis, dysphagia, or swallowing disorder. 11. Clinically active infection with hepatitis B or hepatitis C virus. 12. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator’s judgment, make the patient inappropriate for this study. 13. Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial. 14. Unable or unwilling to swallow tablets.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the incidence of neratinib discontinuations due to diarrhoea within the first 3C (1C = 28 days) in patients with early-stage HER2 overexpressed/amplified (HER2+), hormone receptor-positive (HR+) breast cancer who have completed neoadjuvant/adjuvant trastuzumab-based therapy.;Secondary Objective: - Incidence and time of neratinib discontinuations due to any treatment-emergent adverse event (TEAE). - Diarrhoea due to neratinib: incidence, duration, severity, and treatment interventions. - Incidence of neratinib discontinuation due to any reason. - Incidence of hospitalisations (overall and for diarrhoea). - Incidence of TEAEs and serious adverse events (SAEs) and adverse events of special interest (AESIs, ie, hepatic, cardiac, pulmonary, reproductive and developmental). - Neratinib exposure assessment. - Determine the effect of study treatment on quality of life, as measured by patient reported outcomes, in all treatment arms.;Primary end point(s): Incidence of neratinib discontinuations due to diarrhoea at the end of 3 cycles of neratinib treatment.;Timepoint(s) of evaluation of this end point: When all patients have finished the first 3 months of treatment (July 2024). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence and time to neratinib discontinuations due to any TEAE. - Incidence, cumulative duration and time to first episode of any diarrhoea and grade 3 or higher diarrhoea. - Incidence and time to neratinib discontinuation due to any reason. - Incidence of hospitalisations due to any reason and diarrhoea. - Incidence of TEAEs and SAEs that included AESIs (i.e. hepatic, cardiac, pulmonary, reproductive and developmental). - Incidence of Neratinib dose modifications (reductions and dose holds), and dose intensity. - FACT B and EQ5D-5L questionnaires.;Timepoint(s) of evaluation of this end point: When all patients have finished all treatment (May 2025). | — |
Countries
France, Italy, Spain
Contacts
Public ContactClinical Operations Department
GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
Outcome results
None listed