NERATINIB for HER2-positive breast cancer | Hormone receptor-positive early-stage breast cancer

Inclusion criteria

• {"criterion_text":"- Male or female patient ≥18 years of age at signing of informed consent.\n- Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, i.e., 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 his female partner to use a highly effective method of contraception (i.e., 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.\n- Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events (AEs) related to prior therapies (excluding alopecia, neuropathy, and nail changes).\n- Provide written, informed consent to participate in the study and follow the study procedures.\n- 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). (Clarification note: in patients with surgery as their first treatment approach, the pathological stage will be used; in patients receiving neoadjuvant therapy, the higher staging will be used).\n- Documented HER2-positive disease based on local laboratory determination according to ASCO/CAP 2018 criteria.\n- Documented hormone receptor-positive (HR+) disease, defined as oestrogen receptor (ER) and/or progesterone receptor (PR) ≥1% based on local laboratory determination.\n- 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).\n- 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.\n- Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).\n- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.\n- Negative β-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 ≥ 12 months without menses, in the absence of endocrine or anti-endocrine therapies]."}

Exclusion criteria

• {"criterion_text":"- Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.\n- Significant chronic gastrointestinal disorder with diarrhoea as a major symptom (eg, Crohn’s disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] diarrhoea of any aetiology at baseline); or gastroparesis, dysphagia, or swallowing disorder.\n- Clinically active infection with hepatitis B or hepatitis C virus.\n- 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.\n- Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.\n- Unable or unwilling to swallow tablets.\n- Currently receiving chemotherapy, radiation therapy, immunotherapy, or biological therapy for breast cancer (adjuvant endocrine therapy is allowed).\n- Major surgery within <30 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy <14 days prior to the initiation of investigational products.\n- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrolment, or ventricular arrhythmia.\n- QTc interval >0.450 seconds (males) or >0.470 (females) or known history of QTc prolongation or Torsade de Pointes (TdP).\n- Screening laboratory assessments outside the following limits: Laboratory Parameters/ Required Limit for Exclusion. Absolute neutrophil count (ANC): < or =1,000/µl (< or =1.0 x 109/L). Platelet count: < or =100,000/µl (< or =100 x 109/L). Hemoglobin: < or =9 g/dL. Total bilirubin: >1.5 x institutional upper limit of normal (ULN) (in case of known Gilbert’s syndrome, <2 x ULN is allowed). Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT): >2.5 x institutional ULN. Creatinine: Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formulaa or Modification of Diet in Renal Disease [MDRD] formulab). a: Cockcroft and Gault, 1976. b: Levey et al, 1999\n- Active, unresolved infections.\n- Patients with a second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Patients with other non-mammary malignancies must have been disease free for at least 5 years.\n- Currently pregnant or breast-feeding."}

Primary endpoints

• {"endpoint_text":"- Incidence of neratinib discontinuations due to diarrhoea at the end of 3 cycles of neratinib treatment.","definition_or_measurement_approach":"Incidence of discontinuations due to diarrhoea within the first 3 cycles (1 cycle = 28 days); measured as proportion of patients who discontinue neratinib for diarrhoea by end of cycle 3."}

Secondary endpoints

• {"endpoint_text":"- Incidence and time to neratinib discontinuations due to any TEAE.","definition_or_measurement_approach":"Incidence and time-to-event (time from treatment start to discontinuation) for discontinuations due to any treatment-emergent adverse event (TEAE)."}
• {"endpoint_text":"- Incidence, cumulative duration and time to first episode of any diarrhoea and grade 3 or higher diarrhoea.","definition_or_measurement_approach":"Incidence, cumulative duration (days), and time to first episode for any diarrhoea and for diarrhoea Grade ≥3 (CTCAE v5.0)."}
• {"endpoint_text":"- Incidence and time to neratinib discontinuation due to any reason.","definition_or_measurement_approach":"Incidence and time-to-discontinuation (any cause) measured from first dose to date of discontinuation."}
• {"endpoint_text":"- Incidence of hospitalisations due to any reason and diarrhoea.","definition_or_measurement_approach":"Incidence of hospital admissions overall and those attributed to diarrhoea."}
• {"endpoint_text":"- Incidence of TEAEs and SAEs that included AESIs (i.e. hepatic, cardiac, pulmonary, reproductive and developmental).","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) by category (hepatic, cardiac, pulmonary, reproductive, developmental)."}
• {"endpoint_text":"- Incidence of Neratinib dose modifications (reductions and dose holds), and dose intensity.","definition_or_measurement_approach":"Frequency of dose reductions and dose holds, and calculation of dose intensity over treatment period."}
• {"endpoint_text":"- FACT B and EQ5D-5L questionnaires.","definition_or_measurement_approach":"Patient-reported outcome measures using FACT-B and EQ-5D-5L instruments to assess quality of life across arms."}

Spain

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

05-11-2024

Processing Time Days

14

Number Of Participants

155

Croatia

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

10-12-2024

Processing Time Days

49

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

20

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

18-11-2024

Processing Time Days

27

Number Of Participants

6

Primary sponsor

Full Name

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Hospital Universitario Fundacion Jimenez Diaz","duties_or_roles":"Pathology central laboratory.","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Lodilat Logistica S.L.","duties_or_roles":"Labelling, distribution and storage of medication. Transport of biological samples.","organisation_type":"Pharmaceutical company"}