Neratinib in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Rochester, Minnesota: 13-008111
  • NCT ID:

    NCT01670877
  • Sponsor Protocol Number:

    201209135

About this study

This phase II study will test cancer to see if it has a HER2 mutation and, if so, see how HER2 mutated cancer responds to treatment with neratinib.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria for Pre-registration:

  • Histologically or cytologically confirmed HER2-negative (0 or 1+ by IHC or non-amplified by FISH) breast cancer that is stage IV.
  • There is no limitation on the number of prior lines of systemic therapy.
  • Presence of measurable or non-measurable disease by RECIST 1.1.
  • At least 18 years of age. ECOG performance status ≤ 2. Adequate organ function as defined below within 8 weeks of pre-registration:
    • Serum creatinine ≤ 1.5 x ULN
    • Total bilirubin ≤ 1.5 x ULN (in case of known Gilbert's syndrome, < 2 x ULN is allowed)
    • AST and ALT ≤ 3 x ULN
  • Able to understand and willing to sign an IRB approved written informed consent document.

Note: HER2 mutation testing may be performed while the patient is receiving active systemic therapy for metastatic breast cancer so that the result can be used to determine eligibility for study drug therapy in the future.

Exclusion Criteria for Pre-registration:

  • Testing for LVEF is not required for pre-registration, but patient must not have a recent LVEF < LLN or have symptoms of congestive heart failure.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Acute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment).
  • History of significant cardiac disease, cardiac risk factors, or uncontrolled arrhythmias.
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest.

Inclusion Criteria for Registration

  • Tumor tissue tested positive for HER2 mutation.
  • ECOG performance status ≤ 2.
  • Adequate organ function as defined below within 2 weeks of registration:
    • ANC ≥ 1.5 x 10^9/L
    • Platelet count ≥ 100 x 10^9/L
    • Serum creatinine ≤ 1.5 x ULN
    • Total bilirubin ≤ 1.5 x ULN (in case of known Gilbert's syndrome, < 2 x ULN is allowed)
    • AST and ALT ≤ 3 x ULN
  • The patient must have completed radiation therapy and be at least 1 week from the last systemic chemotherapy administration, with adequate recovery of bone marrow and organ functions, before starting neratinib.
  • Presence of disease progression on the most recent disease evaluation.
  • Patients with known brain metastasis are eligible, but must have received radiation and be off steroids and stable (without evidence of disease progression by imaging or exam) for 3 months.
  • QTc interval ≤ 0.450 seconds within 2 weeks of registration.
  • LVEF ≥ institutional ILLN within 4 weeks of registration.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Able to understand and willing to sign an IRB approved written informed consent document.
  • There is no limitation on the number of prior lines of systemic therapy.

Exclusion Criteria for Registration:

  • Currently receiving any other investigational agents or systemic cancer therapy.
  • Currently taking medications and herbal or dietary supplements that are strong cytochrome P450 (CYP) 3A4 inducers or inhibitors. The washout period must have been completed prior to the start of neratinib if the patient was taking any of these agents. If unavoidable, patients taking CYP3A4 inhibitors should be monitored closely.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Acute or currently active/requiring antiviral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment).
  • Pregnant and/or breastfeeding.
  • History of significant cardiac disease, cardiac risk factors, or uncontrolled arrhythmias.
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest.
  • Experiencing grade 2 or greater diarrhea.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015