Clinical Trials /

Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer



This phase II trial studies the side effects of and how well neratinib works in treating older patients with stage IV HER2-positive breast cancer. Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting


Phase 2

Trial Eligibility


Neratinib in Treating Older Patients With Locally Advanced or Metastatic <span class="go-doc-concept go-doc-biomarker">HER2</span>-Positive Breast Cancer


  • Brief Title: Neratinib in Treating Older Patients With Locally Advanced or Metastatic HER2-Positive Breast Cancer
  • Official Title: Phase II Study of Neratinib in Patients 60 and Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02673398

    ORG ID: 15342

    NCI ID: NCI-2015-02282

    Trial Conditions

    HER2 Positive Breast Carcinoma

    Recurrent Breast Carcinoma

    Stage IIIA Breast Cancer

    Stage IIIB Breast Cancer

    Stage IIIC Breast Cancer

    Stage IV Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Neratinib HKI-272 Treatment (neratinib)

    Trial Purpose

    This phase II trial studies the side effects of and how well neratinib works in treating
    older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer
    that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or
    has spread to other places in the body (metastatic). Neratinib may stop the growth of tumor
    cells by blocking some of the enzymes needed for cell growth.

    Detailed Description


    I. To estimate the safety and tolerability of neratinib in adults age 60 or older with
    locally advanced or metastatic HER2 over-expressing breast cancer.


    I. To describe the full toxicity profile including all grade toxicities measured by National
    Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.

    II. To estimate the rate of all grades of gastrointestinal (GI) toxicities such as diarrhea,
    nausea, and vomiting.

    III. To estimate the rate of dose reduction, delays and discontinuation related to study

    IV. To describe pharmacokinetic parameters of neratinib in adults 60 and older. V. To
    estimate overall response rate (ORR) and clinical benefit rate (CBR) defined by Response
    Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    VI. To estimate event free survival (EFS), progression-free survival (PFS) and overall
    survival (OS).

    VII. To evaluate the role of cancer-specific geriatric assessment tool in predicting
    treatment toxicities.

    VIII. To estimate adherence rate to neratinib in older adults (percentage of doses of
    neratinib taken).

    IX. To explore the association of pharmacokinetic (PK) parameters and geriatric assessment

    X. To explore if serum biomarkers of aging (interleukin [IL]-6, C-reactive protein [CRP],
    and D-dimer) are associated with treatment toxicities.


    Patients receive neratinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28
    days in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up for 30 days and then
    periodically thereafter.

    Trial Arms

    Name Type Description Interventions
    Treatment (neratinib) Experimental Patients receive neratinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Neratinib

    Eligibility Criteria

    Inclusion Criteria:

    - Eastern Cooperative Oncology Group (ECOG) performance 0-2

    - Life expectancy of greater than 12 weeks

    - Histologically or cytologically proven metastatic breast cancer (metastases can be
    proven with imaging results in certain circumstances provided that the initial tumor
    was demonstrated histologically)

    - Locally advanced Her2/Neu positive breast cancer for patients who declined
    conventional treatment with combination chemotherapy and anti-Her2 therapy

    - HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of
    American Pathologists (CAP) guidelines

    - If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization
    (FISH), but activating somatic mutations of HER2 gene identified through genomic
    sequencing (Clinical Laboratory Improvement Act [CLIA] certified lab test): missense
    substitutions (G776V, D769H, E757A, L869R, L841V, L755S, V777L, P780ins,);
    insertions/deletions (A775_G776insYVMA, p780_Y781insGSP; 755_757del)

    - There is no limitation on the number of prior lines of systemic therapy or
    HER2-targeted therapies

    - Both measurable as well as non-measurable disease will be allowed

    - Hemoglobin >= 10g/dL (after transfusion, if necessary)

    - Total bilirubin within normal institutional limits

    - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
    [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 2.5 X institutional upper limit of normal

    - Creatinine clearance >= 30 mL/min as calculated by Cockroft-Gault formula

    - Baseline left ventricular ejection fraction (LVEF) >= 50% as evaluated by
    echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)

    - All grade >= 2 toxicities other than alopecia from prior therapy have resolved by the
    time of study commencement

    - Patient must have completed radiation therapy with adequate recovery of bone marrow
    and organ functions, before starting neratinib

    - Patient with stable or treated brain metastases who do not require steroid are

    - Provide written, informed consent to participate in the study and follow the study

    Exclusion Criteria:

    - Prior treatment with neratinib

    - Concurrent usage of other investigational agents, chemotherapy, or hormone therapy;
    prior chemotherapy, hormonal therapy, targeted therapy, and investigational agents
    are allowed but all toxicities grade >= 2 must have resolved by the time of study
    commencement (except alopecia)

    - Any major surgery =< 28 days prior to the initiation of investigational products, or
    received anti-cancer therapy (including chemotherapy, biological therapy, hormonal
    therapy, investigational agents, or other anti-cancer therapy) administered =< 14
    days prior to initiation of investigational products

    - Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart
    failure (New York Heart Association functional classification of >= 2, including
    individuals who currently use digitalis specifically for congestive heart failure ),
    unstable angina, myocardial infarction within 12 month of enrollment or ventricular

    - Concurrent use of digoxin due to cardiac disease

    - Corrected QT (QTc) interval >= 450 milliseconds in men and >= 470 milliseconds in
    women within 2 weeks of registration or known history of QTc prolongation or Torsades
    de Pointes

    - Inability to take oral medication

    - Known hypersensitivity to any component of the investigational product

    - Other malignancy within the past 3 years with the exception of: a) adequately treated
    basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) cervix or
    vulva carcinoma in situ; c) cancer considered cured by surgical resection or unlikely
    to impact survival during the duration of the study, such as localized transitional
    cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas

    - Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g.,
    Crohn's disease, malabsorption, or grade >= 2 NCI CTCAE v.4.0 diarrhea of any
    etiology at baseline)

    - Known clinically active infection with hepatitis B or hepatitis C virus

    - Evidence of significant medical illness, abnormal laboratory finding or psychiatric
    illness/social situations that would, in the Investigator's judgment, makes the
    patient inappropriate for this study

    Minimum Eligible Age: 60 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of grade 2 or higher toxicities, graded according to the NCI CTCAE v4.0

    Secondary Outcome Measures

    Adherence, as defined by pill count

    CBR, defined as the proportion of patients who achieved overall tumor response (CR or PR) or stable disease (SD) for at least 24 weeks, measured by RECIST

    IL-6 (interleukin-6), CRP (C reactive protein ), and D-dimer will be measured and descriptive statistics provided.


    Geriatric assessment score

    Incidence of all toxicities, graded according to the NCI CTCAE v4.0

    Incidence of GI toxicities such as diarrhea, nausea and vomiting, graded according to the NCI CTCAE v4.0

    ORR, measured by RECIST



    Clearance will be estimated using population PK methods.

    Volume of distribution will be estimated using population PK methods.

    Rate of dose reduction

    Rate of holds

    Rate of hospitalizations

    Trial Keywords