Clinical trial NCT01423123 (phase 1, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: paclitaxel, neratinib
SMILES: [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC, CCOC1=C(NC(=O)\C=C\CN(C)C)C=C2C(NC3=CC=C(OCC4=CC=CC=N4)C(Cl)=C3)=C(C=NC2=C1)C#N
Eligibility criteria:

        Inclusion Criteria:

          -  Co-morbid conditions should be taken into consideration, but not the diagnosis of
             metastatic breast cancer.

          -  Patients of reproductive potential must agree to use an effective non-hormonal method
             of contraception during therapy and for at least 6 months after the last dose of study
             therapy.

          -  The ECOG performance status must be 0, 1, or 2.

          -  Patients must have the ability to swallow oral medication.

          -  Patients must have histologic or cytologic confirmation of the diagnosis of invasive
             adenocarcinoma of the breast.

          -  There must be documentation that the patient has evidence (measurable or
             non-measurable) of metastatic breast cancer. Histologic confirmation of metastatic
             disease is not required.

          -  Patients must have ER analysis performed on the primary tumor prior to study entry. If
             ER analysis is negative, then PgR analysis must also be performed. (Patients are
             eligible with either hormone receptor-positive or hormone receptor-negative tumors.)

          -  Breast cancer must be determined to be HER2-positive prior to study entry. Assays
             using FISH or CISH require gene amplification. Assays using IHC require a strongly
             positive (3+) staining score.

          -  At the time of study entry, blood counts performed within 4 weeks prior to study entry
             must meet the following criteria: ANC must be greater than or equal to 1000/mm3;
             Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be
             greater than or equal to 9 g/dL

          -  The following criteria for evidence of adequate hepatic function performed within 4
             weeks prior to study entry must be met: total bilirubin must be less than or equal to
             1.5 x ULN; AST and ALT must be less than or equal to 2.5 x ULN for the lab or less
             than or equal to 5 x ULN if liver metastasis

          -  Serum creatinine performed within 4 weeks prior to study entry must be less than or
             equal to 1.5 x ULN for the lab.

          -  The LVEF assessment by 2-D echocardiogram or MUGA scan performed within 90 days prior
             to study entry must be greater than or equal to 50% regardless of the facility's LLN.

        Exclusion Criteria:

          -  Previous therapy with neratinib for any malignancy.

          -  Symptomatic brain metastases or brain metastases requiring chronic steroids to control
             symptoms.

          -  Active hepatitis B or hepatitis C with abnormal liver function tests.

          -  Intrinsic lung disease resulting in dyspnea.

          -  Active infection or chronic infection requiring chronic suppressive antibiotics.

          -  Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of
             the stomach or small bowel, or other disease or condition significantly affecting
             gastrointestinal function.

          -  Persistent greater than or equal to grade 2 diarrhea regardless of etiology.

          -  Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI
             CTCAE v3.0.

          -  Conditions that would prohibit intermittent administration of corticosteroids for
             paclitaxel premedication.

          -  Chronic daily treatment with corticosteroids with a dose of greater than or equal to
             10 mg/day methylprednisolone equivalent (excluding inhaled steroids).

          -  Uncontrolled hypertension defined as a systolic BP greater than 150 mmHg or diastolic
             BP greater than 90 mmHg, with or without anti-hypertensive medications (Patients with
             hypertension that is well controlled on medication are eligible.)

          -  Cardiac disease (history of and/or active disease) that would preclude the use of any
             of the drugs included in the treatment regimen. This includes but is not confined to:
             Active cardiac disease: symptomatic angina pectoris within the past 90 days that
             required the initiation of or increase in anti-anginal medication or other
             intervention; ventricular arrhythmias except for benign premature ventricular
             contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not
             controlled with medication; conduction abnormality requiring a pacemaker; valvular
             disease with documented compromise in cardiac function; and symptomatic pericarditis.
             History of cardiac disease: myocardial infarction documented by elevated cardiac
             enzymes or persistent regional wall abnormalities on assessment of LV function;
             history of documented CHF; and documented cardiomyopathy

          -  Other nonmalignant systemic disease that would preclude the patient from receiving
             study treatment or would prevent required follow up.

          -  Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be
             performed within 14 days prior to study entry according to institutional standards for
             women of childbearing potential.)

          -  The investigator should assess the patient to determine if she has any psychiatric or
             addictive disorder or other condition that, in the opinion of the investigator, would
             preclude her from meeting the study requirements.

          -  Use of any investigational agent within 4 weeks prior to study entry.