Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
|Breast Neoplasms HER2/Neu Positive Geriatric Health Services||Drug: Lapatinib Drug: Trastuzumab Other: laboratory biomarker analysis Other: pharmacological study||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer|
- Grade 3 or higher non-hematological toxicities and symptomatic congestive heart failure (as defined by NCI CTCAE v.4.0) [ Time Frame: Until 30 days after last dose of treatment ]Tables will be created to summarize the toxicities and side effects for each dose schedule by dose, course, organ and severity for all patients. All serious adverse events and other serious toxicities will be described on a patient by patient basis. Numbers of cycles received and dose reductions will be tabulated by dose. Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
- All toxicities associated with the combinations as measured by NCI CTCAE v. 4.0 [ Time Frame: Until 30 days after last dose of treatment ]Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
- Dose reductions, dose interruptions, dose discontinuations [ Time Frame: While on treatment ]Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
- Tumor response (using RECIST criteria) [ Time Frame: Up to 8 years ]Response rate (complete response [CR] + partial response [PR]) and clinical benefit rate (CR + PR + stable disease [SD]) and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.
- Progression-free survival [ Time Frame: From start of treatment until documented disease progression or death ]
- Overall survival [ Time Frame: From start of treatment until death from any cause ]
- Pharmacokinetic parameters of lapatinib, including trough levels and area under curve (AUC) [ Time Frame: Day 15 of course 1 and days 1 and 8 of course 2 ]AUC will be calculated and reported using standard descriptive statistics.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2019 (Final data collection date for primary outcome measure)|
Experimental: Lapatinib and trastuzumab
Patients receive lapatinib ditosylate PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
250 mg tablets
Other Names:Drug: Trastuzumab
Other Name: HerceptinOther: laboratory biomarker analysis
Other Name: Correlative studiesOther: pharmacological study
Other Name: Correlative studies
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01273610
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|City of Hope Antelope Valley|
|Lancaster, California, United States, 93534|
|South Pasadena Cancer Center|
|Pasadena, California, United States, 91030|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center, University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27704|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Arti Hurria, MD||City of Hope Medical Center|