Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT01273610

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-20
• Study Completion Date: 2026-05-19

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.

Conditions

Breast Neoplasms; HER2/Neu Positive; Geriatric Health Services

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

250 mg tablets

Trastuzumab

Intervention Type: DRUG

Intravenous injection

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

Lapatinib

250 mg tablets

Intervention Type: DRUG

Trastuzumab

Intravenous injection

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Other Intervention Names

Tykerb; Tyverb; GSK572016; GW-572016; GW2016; Herceptin; Correlative studies; Correlative studies

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
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/aspartate aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine clearance >= 30 mL/min as measured using either the Cockcroft-Gault method or 24-hour creatinine clearance
• The above tests must be obtained within 14 days of study treatment
• Cardiac ejection fraction >= 50% as measured by echocardiogram or multiple gated acquisition scan (MUGA) scan
• The ability to swallow and retain oral medication
• Prior treatment with lapatinib or trastuzumab are allowed, provided that the agents have never been given in combination
• Any number of prior cancer treatments, including investigational agents, chemotherapy, hormone therapy, or targeted therapy are allowed
• All patients must have the ability to understand and the willingness to sign a written informed consent

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%)
• High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrio-ventricular [AV]-block, supraventricular tachycardias which are not adequately rate-controlled)
• Angina pectoris requiring antianginal medications
• Evidence of transmural infarction on electrocardiogram (ECG)
• Clinically significant valvular heart disease
• Poorly controlled hypertension (e.g. systolic > 180 mm HG or diastolic > 100 mm Hg)
• Any other cardiac condition, which in the opinion of the treating physician would make this protocol unreasonably hazardous for the patient
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daneng Li, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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

Countries

United States

References

Hurria A, Gupta S, Zauderer M, Zuckerman EL, Cohen HJ, Muss H, Rodin M, Panageas KS, Holland JC, Saltz L, Kris MG, Noy A, Gomez J, Jakubowski A, Hudis C, Kornblith AB. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005 Nov 1;104(9):1998-2005. doi: 10.1002/cncr.21422.

Reference Type: BACKGROUND

PMID: 16206252 (View on PubMed)

Hurria A, Lichtman SM. Pharmacokinetics of chemotherapy in the older patient. Cancer Control. 2007 Jan;14(1):32-43. doi: 10.1177/107327480701400105.

Reference Type: BACKGROUND

PMID: 17242669 (View on PubMed)

Kimmick GG, Fleming R, Muss HB, Balducci L. Cancer chemotherapy in older adults. A tolerability perspective. Drugs Aging. 1997 Jan;10(1):34-49. doi: 10.2165/00002512-199710010-00004.

Reference Type: BACKGROUND

PMID: 9111706 (View on PubMed)

Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol. 2004 Nov 15;22(22):4626-31. doi: 10.1200/JCO.2004.02.175.

Reference Type: BACKGROUND

PMID: 15542812 (View on PubMed)

Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. doi: 10.1200/JCO.2008.21.4437. Epub 2010 Feb 1.

Reference Type: BACKGROUND

PMID: 20124187 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2011-00116

Identifier Type: REGISTRY

Identifier Source: secondary_id

10112

Identifier Type: -

Identifier Source: org_study_id