This phase II trial studies the side effects and how well lapatinib ditosylate and trastuzumab work in treating older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or to other parts of the body (metastatic). Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or tumor cancer-killing substances to them. Giving lapatinib ditosylate together with trastuzumab may kill more tumor cells.
PRIMARY OBJECTIVES: I. To estimate the safety and tolerability of the combination of trastuzumab and lapatinib (lapatinib ditosylate) in adults age 60 or older with locally advanced or metastatic breast cancer. SECONDARY OBJECTIVES: I. To describe the full toxicity profile including all grades; to estimate the rate of all grades of cardiac toxicity; to estimate the rate of all grades of diarrhea, nausea, and vomiting. II. To describe the pharmacokinetic parameters of lapatinib in older adults. III. To estimate objective response rate and clinical benefit rate as defined by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. IV. To estimate median progression-free and overall survival. V. To explore factors other than chronological age that can affect toxicity rates as identified using a cancer-specific geriatric assessment. VI. To estimate rates of adherence to lapatinib in older adults. OUTLINE: Patients receive lapatinib ditosylate orally (PO) once daily (QD) and trastuzumab intravenously (IV) over 30-90 minutes once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then periodically thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
250 mg tablets
Intravenous injection
City of Hope Medical Center
Duarte, California, United States
City of Hope Antelope Valley
Lancaster, California, United States
South Pasadena Cancer Center
Pasadena, California, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Lineberger Comprehensive Cancer Center, University of North Carolina
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Case Western Reserve University
Cleveland, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Percent of Participants With Grade 3 or Higher Non-hematological Toxicities and Symptomatic Congestive Heart Failure
Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 3 or higher toxicities attributed to lapatinib or trastuzumab.
Time frame: Until 30 days after last dose of treatment, an average of 8 months
Percent of Participants With a Dose Modifications
Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated. A dose modification was defined as a hold (participant started the dose later than scheduled), reduction (subject was given a lower dose than originally scheduled), or discontinuation (subject stopped treatment) of lapatinib.
Time frame: While on treatment, up to 4.5 years
Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST: Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: While on treatment, up to 4.5 years
Median Progression-free Survival (PFS)
Median PFS and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated across all ages per protocol plan. Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions.
Time frame: From the date treatment begins until the first date on which recurrence, progression or death due to any cause, with an average follow up of 1 year.
Median Overall Survival (OS)
OS will be estimated using the product limit method of Kaplan and Meier across all ages per protocol plan.
Time frame: Time from start of treatment to death due to any cause, with average follow up of 4.5 years
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