Incidence and Severity of Diarrhea in Patients With HER2 Positive Breast Cancer Treated With Trastuzumab and Neratinib
- Conditions
- HER2-positive Breast CancerStage II Breast Cancer AJCC v6 and v7Breast AdenocarcinomaStage IIA Breast Cancer AJCC v6 and v7Stage IIIC Breast Cancer AJCC v7Stage IIIB Breast Cancer AJCC v7Stage IIB Breast Cancer AJCC v6 and v7Stage III Breast Cancer AJCC v7Stage IIIA Breast Cancer AJCC v7
- Interventions
- Biological: Trastuzumab
- Registration Number
- NCT03094052
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
This phase II trial studies the incidence and severity of diarrhea in patients with stage II-IIIC HER2 Positive breast cancer treated with trastuzumab and neratinib. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and neratinib may work better in treating patients with stage II-IIIC HER2 positive breast cancer.
- Detailed Description
PRIMARY OBJECTIVE:
I. To characterize the incidence and severity of diarrhea in patients with early stage breast cancer receiving adjuvant neratinib with or without trastuzumab in the setting of anti-diarrheal strategies.
SECONDARY OBJECTIVES:
I. To evaluate the incidence of grade 3 or higher diarrhea using the dose-escalation strategy and anti-diarrhea medications as needed (prn) in patients who received prior trastuzumab emtansine (T-DM1).
II. To assess neratinib adherence, holds, delays, and early discontinuation throughout the course of study therapy which includes patients receiving neratinib for \> 1 year.
III. To assess overall toxicity including constipation and cardiac toxicity with concomitant neratinib and trastuzumab.
OUTLINE: This is a dose-escalation study of neratinib. Patients receive one of the following treatment regimen:
NERATINIB MONOTHERAPY: Patients receive neratinib orally (PO) once daily (QD) on days 1-21. Cycles repeats every 21 days for up to 55 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive loperamide and/or diphenoxylate hydrochloride/atropine sulfate as needed per physician discretion for symptom management.
NERATINIB AND TRASTUZUMAB: Patients receive neratinib PO QD on days 1-21. Patients also receive trastuzumab maintenance therapy as determined by treating physician. Treatment repeats every 21 days for up to 55 weeks in the absence of disease progression or unacceptable toxicity. After completion of trastuzumab treatment, patients may continue on neratinib monotherapy for the remainder of the 55 weeks. Patients may receive loperamide and/or diphenoxylate hydrochloride/atropine sulfate as needed per physician discretion for symptom management.
After completion of studies treatment, patients are followed up for 28 days.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (Neratinib) Trastuzumab Patients will receive up to 240mg neratinib to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Patients will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks. Treatment (Neratinib) Diphenoxylate Hydrochloride/Atropine Sulfate Patients will receive up to 240mg neratinib to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Patients will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks. Treatment (Neratinib) Neratinib Patients will receive up to 240mg neratinib to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Patients will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks. Treatment (Neratinib) Loperamide Patients will receive up to 240mg neratinib to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Patients will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Grade 3 or Greater Diarrhea Up to 6 weeks Percentage of participants with clinically assessed grade 3 or greater diarrhea reported within the first 2 cycles (each cycle is 21 days) of neratinib while using anti-diarrheal strategies. Reports of diarrhea will be graded according to NCI CTCAE version 4.0.
Percentage of Participants With Multiple Anti-diarrheal Medications Up to 55 weeks Percentage of patients requiring multiple anti-diarrheal medications will be reported
Percentage of Participants With Treatment-related Adverse Events Up to 55 weeks Percentage of participants with reported serious adverse events and adverse events of interest of any grade that have been determined to be related to the anti-diarrhea treatment will be reported by worst grade and associated toxicity.
Number of Participants With Neratinib Dose Holds Up to 55 weeks The number of participants who experienced a dose hold of neratinib during the course of study therapy will be reported
Number of Participants Who Discontinued Neratinib Early Up to 55 weeks The number of participants who discontinued neratinib earlier than expected during the course of study therapy will be reported
Number of Participants With Neratinib Dose-reductions Up to 55 weeks The number of participants whose dose was reduced at any time during the course of therapy will be reported
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of California, San Francisco
🇺🇸San Francisco, California, United States