- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01557764
Lapatinib With Trastuzumab in Treating Patients With HER2-Negative/HER2 Mutant Metastatic Breast Cancer
A Phase II Study of Lapatinib in Combination With Trastuzumab in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3.0 x IULN with/without liver metastases
- Creatinine =< 1.5 x IULN
- Patient must have a left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (ILLN) to be eligible for study treatment; to avoid the cost of screening, patients with known recent LVEF < LLN or symptoms of congestive heart failure are not eligible for registration
- Women of childbearing potential (WOCBP) 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
- Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an institutional review board (IRB) approved written informed consent document
- Patients with known treated brain metastasis are eligible, but must have received radiation and be off steroids and stable for 3 months
- Patients meeting all inclusion criteria listed above and exclusion criteria will be registered to undergo HER2 mutation analysis; only patients with mutations in HER2 either in the primary or metastatic tumor are eligible for study therapy with lapatinib and trastuzumab; those without mutations in HER2 are not eligible for study drug therapy; information and tissue collected from patients without HER2 mutations will be used for molecular epidemiology studies of HER2 negative breast cancer
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PFS of patients treated with lapatinib and trastuzumab
Time Frame: 2 years
|
Assessed using RECIST guidelines version 1.1
|
2 years
|
Correlation of HER2 mutation with histology subtype (invasive lobular vs. invasive ductal cancer)
Time Frame: Baseline
|
Baseline
|
|
Correlation of HER2 mutation with tumor grade (1-2 vs. 3)
Time Frame: Baseline
|
Baseline
|
|
Correlation of HER2 mutation with tumor staging at initial diagnosis (I vs. II or III vs. IV)
Time Frame: Baseline
|
Baseline
|
|
Correlation of HER2 mutation with disease free survival
Time Frame: 2 years
|
2 years
|
|
Occurrence of HER2 mutation in paired primary and metastatic sites
Time Frame: Baseline
|
Baseline
|
Collaborators and Investigators
Investigators
- Principal Investigator: Cynthia Ma, M.D., Ph.D., Washington University School of Medicine
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Trastuzumab
- Antibodies
- Antibodies, Monoclonal
- Lapatinib
Other Study ID Numbers
- 201206025
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Neoplasms
-
Emory UniversityEisai Inc.TerminatedBreast Cancer | Breast Neoplasms | Breast Tumors | Neoplasms, Breast | Cancer of the Breast | Tumors, BreastUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
G1 Therapeutics, Inc.TerminatedBreast Cancer | Breast Neoplasm | Triple-Negative Breast Cancer | Triple-Negative Breast NeoplasmsUnited States, Bulgaria, Croatia, Slovenia, Serbia, Belgium, North Macedonia, Slovakia
-
Seagen Inc.CompletedTriple Negative Breast Neoplasms | Hormone Receptor Positive Breast Neoplasms | HER2 Positive Breast Neoplasms | HER2 Mutations Breast NeoplasmsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Celgene CorporationTerminatedInflammatory Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Recurrent Breast Cancer | HER2-negative Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedInflammatory Breast Cancer | Male Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Providence Health & ServicesBrooklyn ImmunoTherapeutics, LLCActive, not recruitingBreast Neoplasm | Triple Negative Breast Cancer | Breast Neoplasm, MaleUnited States
-
Dana-Farber Cancer InstituteConquer Cancer FoundationRecruitingBreast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | HER2-positive Breast Cancer | Inflammatory Breast Cancer | Hormone Receptor Positive Malignant Neoplasm of BreastUnited States
-
GlaxoSmithKlineCompletedNeoplasms, BreastUnited States, Spain, Israel, Canada, Belgium, United Kingdom, France, Tunisia
-
GlaxoSmithKlineCompletedNeoplasms, BreastUnited States, Canada, Germany, Spain, Taiwan, Belgium, Philippines, Israel, Hong Kong, Thailand, Pakistan, Russian Federation, Italy, Romania, China, France, Peru, United Kingdom, Czech Republic, Australia, Chile, Korea, Republic of and more
Clinical Trials on trastuzumab
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingBreast Ductal Carcinoma In SituUnited States, Canada, Puerto Rico, Korea, Republic of
-
Tanvex BioPharma USA, Inc.CompletedBreast Cancer | Breast Neoplasms | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Early-stage Breast CancerBelarus, Chile, Georgia, Hungary, India, Mexico, Peru, Philippines, Russian Federation, Ukraine
-
Spanish Breast Cancer Research GroupCompleted
-
Fudan UniversityHoffmann-La RocheUnknown
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRecruitingHER2-positive Breast Cancer | Early-stage Breast Cancer | Adjuvant Treatment After Trastuzumab | RCB Classification 1-2 | NeratiniChina
-
Orano Med LLCCompletedStomach Neoplasms | Breast Neoplasms | Pancreatic Neoplasms | Ovarian Neoplasms | Peritoneal NeoplasmsUnited States
-
National Cancer Institute (NCI)Active, not recruitingMale Breast Carcinoma | Stage IIA Breast Cancer AJCC v6 and v7 | Stage IIB Breast Cancer AJCC v6 and v7 | Stage IIIA Breast Cancer AJCC v7 | Stage IIIB Breast Cancer AJCC v7 | Stage IIIC Breast Cancer AJCC v7United States, Puerto Rico
-
Samsung Bioepis Co., Ltd.TerminatedBreast NeoplasmsUkraine, Romania, Russian Federation, France, Bulgaria, Czechia, Poland
-
University Medical Center GroningenCompleted
-
Fudan UniversityCompleted