HER2 amplified (HER2+) stage 1 through stage 4 primary adenocarcinoma of the breast MedDRA version: 20.0 Level: PT Classification code 10006199 Term: Breast cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10006200 Term: Breast cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classif
Conditions
Interventions
Sponsors
Puma Biotechnology, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years at signing of informed consent. 2. Histologically confirmed stage 1 through stage 4 primary adenocarcinoma of the breast. 3. Documented HER2 overexpression or gene-amplified tumor by a validated approved method. 4. Patients with confirmed stage 1 to 3c breast cancer receiving neratinib monotherapy must have completed a course of prior adjuvant trastuzumab or experienced side effects that resulted in early discontinuation of trastuzumab that have since resolved. 5. Patients with mBC must have had at least 2 prior HER2-directed regimens. 6. Left ventricular ejection fraction (LVEF) >=50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO). 7. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1. 8. 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 >=12 months without menses, in the absence of endocrine or anti-endocrine therapies. 9. 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 partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 28 days after the last dose of the investigational products. Men (male patient) with a female partner of childbearing potential must agree and commit to use condom and the female partner must agree and commit 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 investigational products. 10. Recovery (i.e., to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes). 11. No major bleeding diathesis or use of anticoagulants that would pose a high risk for endoscopic procedure. 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 4 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Patients with confirmed stage 1 through stage 3c breast cancer currently receiving chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer. 2. Patients with mBC that have received prior capecitabine or HER2 directed TKI therapy. 3. Currently using drugs that have been implicated as causing microscopic colitis/watery diarrhea, such as acarbose, aspirin, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), histamine H2 receptor antagonists, selective serotonin reuptake inhibitors, and ticlopidine. 4. Major surgery within =2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia. 6. QTc interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP). 7. Diagnosis of inflammatory bowel disease. 8. Screening laboratory assessments outside the following limits: - 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 (>5 x ULN if liver metastases are present in mBC patients) - Creatinine: Creatinine clearance =1.5 9. Active, unresolved infections. 10. 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. 11. Currently pregnant or breast-feeding. 12. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn’s disease, malabsorption, or Grade >=2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline). 13. Clinically active infection with hepatitis B or hepatitis C virus. 14. 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. 15. Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial. 16. Unable or unwilling to swallow tablets.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize and understand colon pathogenesis related to neratinib-induced diarrhea through biopsies and images obtained by colonoscopy study. ;Secondary Objective: - To characterize the incidence and severity of diarrhea during the first 28-day cycle. - To analyze changes in serological and fecal inflammatory markers from baseline to second colonoscopy.;Primary end point(s): The primary endpoint is change from baseline in pathological findings in colon biopsies after the first 28 days of neratinib monotherapy.;Timepoint(s) of evaluation of this end point: The primary analysis of pathology findings will be conducted after all patients have completed 2 colonoscopies with associated biopsies. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: - The incidence and severity of diarrhea summarized according to the NCI-CTCAE version 4.0 in the first 28-day cycle of neratinib treatment. - Change from baseline at the time of the first colonoscopy (prior to initiation of therapy with neratinib) to the second study colonoscopy procedure in serological and fecal inflammatory markers.;Timepoint(s) of evaluation of this end point: The primary analysis of the incidence and severity of diarrhea and inflammatory markers will be conducted after all patients have completed 2 colonoscopies and all samples have been collected and analyzed. | — |
Countries
Portugal, United States
Contacts
Public ContactClinical Trial Management
Puma Biotechnology, Inc
Outcome results
None listed