Lapatinib With Trastuzumab in Treating Patients With HER2-Negative/HER2 Mutant Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01557764
Recruitment Status : Withdrawn
First Posted : March 19, 2012
Last Update Posted : July 4, 2013
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: lapatinib ditosylate Biological: trastuzumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Lapatinib in Combination With Trastuzumab in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer
Study Start Date : September 2012
Estimated Primary Completion Date : March 2016
Estimated Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

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.
Drug: lapatinib ditosylate
Given PO
Other Name: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb
Biological: trastuzumab
Given IV
Other Name: anti-c-erB-2, Herceptin, MOAB HER2, MOAB HER2, monoclonal antibody c-erb-2, monoclonal antibody HER2

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. PFS of patients treated with lapatinib and trastuzumab [ Time Frame: 2 years ]
    Assessed using RECIST guidelines version 1.1

  2. Correlation of HER2 mutation with histology subtype (invasive lobular vs. invasive ductal cancer) [ Time Frame: Baseline ]
  3. Correlation of HER2 mutation with tumor grade (1-2 vs. 3) [ Time Frame: Baseline ]
  4. Correlation of HER2 mutation with tumor staging at initial diagnosis (I vs. II or III vs. IV) [ Time Frame: Baseline ]
  5. Correlation of HER2 mutation with disease free survival [ Time Frame: 2 years ]
  6. Occurrence of HER2 mutation in paired primary and metastatic sites [ Time Frame: Baseline ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01557764

Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: Cynthia Ma, M.D., Ph.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine Identifier: NCT01557764     History of Changes
Other Study ID Numbers: 201206025
First Posted: March 19, 2012    Key Record Dates
Last Update Posted: July 4, 2013
Last Verified: July 2013

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action