Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib
- Conditions
- Breast Neoplasms
- Sponsor
- City of Hope Medical Center
- Enrollment
- 40
- Locations
- 8
- Primary Endpoint
- Percent of Participants With Grade 3 or Higher Non-hematological Toxicities and Symptomatic Congestive Heart Failure
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Locally advanced or metastatic Her2/Neu positive breast cancer (defined as immunohistochemistry \[IHC\] 3+ or a fluorescence in situ hybridization \[FISH\] ratio of \>= 2.0); this may be on either a primary tumor or a metastatic site, and there is no time limit from the time the specimen was obtained; locally advanced breast cancer (LABC) includes breast cancers with advanced primary tumors, i.e., large diameter (at least 5 cm) or those with skin and/or chest wall involvement, and advanced regional lymph node involvement; it also includes a rare subgroup, inflammatory breast cancer; in the 2010 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) TNM breast cancer staging system, locally advanced breast cancer (LABC) includes patients with stage III disease; this comprises:
- •Advanced primary tumors (tumors \> 5 cm in greatest dimension \[T3\]; direct extension to the chest wall and/or to the skin \[T4\]: ulceration, skin nodules, and/or edema (including peau d'orange) confined to the same breast, inflammatory breast cancer \[IBC, T4d\])
- •Advanced regional lymph nodes (ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted or clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases \[N2\], ipsilateral infraclavicular \[level III axillary\] lymph nodes, ipsilateral internal mammary lymph node\[s\] with axillary lymph nodes, or ipsilateral supraclavicular lymph nodes \[N3\])
- •Both measurable and non-measurable disease are allowed
- •Life expectancy of greater than 12 weeks
- •Women of child-bearing potential and sexually active men must agree to use adequate contraception prior to study entry for six months following duration of study participation
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky performance status \>= 60%)
- •Hemoglobin \>= 10 g/dL (after transfusion if necessary)
- •Absolute neutrophil count \>= 1,500/mcL
- •Platelets \>= 100,000/mcL
Exclusion Criteria
- •Concurrent investigational treatment, chemotherapy, or targeted therapy; prior chemotherapy, hormonal therapy, targeted therapy, and investigational agents are allowed but all toxicities grade \>= 2 must have resolved by the time of study commencement (except alopecia)
- •Unstable or symptomatic brain metastases (however, patients with stable or treated brain metastases who do not require steroids at doses above those permitted for control of symptoms may be enrolled)
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to lapatinib or trastuzumab; however, patients with a history of infusion reaction to trastuzumab which was controlled with premedication on subsequent infusions without a recurring infusion reaction are eligible
- •Concomitant medications listed are prohibited; inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) not listed can be used with caution
- •Ongoing or active infection (including human immunodeficiency virus \[HIV\]) or psychiatric illness/social situations that would limit compliance with study requirements
- •Inability to take oral medication
- •Malabsorption syndrome, (prior surgical procedures affecting absorption), or inflammatory gastrointestinal (GI) disease (e.g., Crohn's, ulcerative colitis) which in the opinion of the study coordinator is likely to limit normal absorption of the drug
- •Current active 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)
- •Active cardiac disease, defined as (but not limited to):
- •History of documented congestive heart failure (CHF) or systolic dysfunction (left ventricular ejection fraction \[LVEF\] \< 50%)
Arms & Interventions
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.
Intervention: Lapatinib
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.
Intervention: Trastuzumab
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.
Intervention: laboratory biomarker analysis
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.
Intervention: pharmacological study
Outcomes
Primary Outcomes
Percent of Participants With Grade 3 or Higher Non-hematological Toxicities and Symptomatic Congestive Heart Failure
Time Frame: Until 30 days after last dose of treatment, an average of 8 months
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.
Secondary Outcomes
- Number of Participants With Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST)(While on treatment, up to 4.5 years)
- Median Progression-free Survival (PFS)(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)(Time from start of treatment to death due to any cause, with average follow up of 4.5 years)
- Percent of Participants With a Dose Modifications(While on treatment, up to 4.5 years)