A Phase II Study of Lapatinib in Combination With Trastuzumab in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- lapatinib ditosylate
- Conditions
- Breast Neoplasms
- Sponsor
- Washington University School of Medicine
- Primary Endpoint
- Overall clinical benefit rate (CBR; CD + PR + SD) of lapatinib and trastuzumab in patients with breast cancer that carry HER2 mutations
- Status
- Withdrawn
- Last Updated
- 12 years ago
Overview
Brief Summary
This phase II trial studies the effectiveness of lapatinib ditosylate (lapatinib) together with trastuzumab in treating patients with HER2-negative breast cancer that carries HER2 gene mutations. Lapatinib may kill tumor cells by blocking some of the enzymes needed for cell division and growth. Trastuzumab, a monoclonal antibody, may block the ability of tumor cells to grow and spread. Giving lapatinib together with trastuzumab may provide a more effective treatment for patients with this type of cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must have histologically or cytologically confirmed metastatic breast cancer
- •The breast cancer has been tested negative for HER2 (0 or 1+ by immunohistochemistry \[IHC\] or non-amplified by fluorescence in-situ hybridization \[FISH\])
- •Patient may have measurable or evaluable disease
- •If given prior radiotherapy and/or prior chemotherapy, the patient must have completed radiation therapy and be at least 1 week from the last chemotherapy administration, with adequate recovery of bone marrow and organ functions, before starting lapatinib or trastuzumab
- •\* Note that the HER2 sequencing analysis can be performed while patient is receiving other systemic therapies so the results could be used to determine whether the patient is eligible to receive lapatinib and trastuzumab when disease progresses from current therapy
- •Patient must have had at least one lines of systemic therapy for metastatic breast cancer
- •Patient must have disease that progressed on his/her most recent treatment regimen
- •Patient must be \> 18 years of age.
- •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) unless due to Gilbert's syndrome
Exclusion Criteria
- •Patient must not be receiving any other investigational agents
- •Patient must not have an 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
- •Patient must not have 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)
- •Patient must not be pregnant and/or breastfeeding
- •Patient must not have a history of significant cardiac disease, cardiac risk factors, or uncontrolled arrhythmias
- •Patient must not have symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
Arms & Interventions
Treatment (enzyme inhibitor and monoclonal antibody)
Patients receive lapatinib PO QD on days 1-21 and trastuzumab IV over 90 minutes on day 1 of a 21-day cycle. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: lapatinib ditosylate
Treatment (enzyme inhibitor and monoclonal antibody)
Patients receive lapatinib PO QD on days 1-21 and trastuzumab IV over 90 minutes on day 1 of a 21-day cycle. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: trastuzumab
Outcomes
Primary Outcomes
Overall clinical benefit rate (CBR; CD + PR + SD) of lapatinib and trastuzumab in patients with breast cancer that carry HER2 mutations
Time Frame: 6 months
Responses assessed using RECIST guidelines version 1.1; duration of SD must be \>= 6 months; CBR and its 80% confidence interval will be calculated.
Secondary Outcomes
- PFS of patients treated with lapatinib and trastuzumab(2 years)
- Correlation of HER2 mutation with histology subtype (invasive lobular vs. invasive ductal cancer)(Baseline)
- Correlation of HER2 mutation with tumor grade (1-2 vs. 3)(Baseline)
- Correlation of HER2 mutation with tumor staging at initial diagnosis (I vs. II or III vs. IV)(Baseline)
- Correlation of HER2 mutation with disease free survival(2 years)
- Occurrence of HER2 mutation in paired primary and metastatic sites(Baseline)