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

NCT01273610 | Active Not Recruiting Phase 2 Results DMC

• 2 other identifiers: 10112NCI-2011-00116
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

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.

Conditions

Breast Neoplasms; HER2/Neu Positive; Geriatric Health Services

Keywords

Breast Neoplasms; HER2 protein, human; Geriatric Health Services; Antineoplastic Agents, Combined; Geriatric Assessment; Pharmacokinetics; Toxicity; Patient Adherence

Outcome Measures

Primary Outcomes (1)

• 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.

  Until 30 days after last dose of treatment, an average of 8 months

Secondary Outcomes (4)

• Percent of Participants With a Dose Modifications

  While on treatment, up to 4.5 years

• 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

Study Arms (1)

Lapatinib and trastuzumab

EXPERIMENTAL

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.

Drug: Lapatinib; Drug: Trastuzumab; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

Lapatinib DRUG

250 mg tablets

Also known as: Tykerb, Tyverb, GSK572016, GW-572016, GW2016

Lapatinib and trastuzumab

Trastuzumab DRUG

Intravenous injection

Also known as: Herceptin

Lapatinib and trastuzumab

laboratory biomarker analysis OTHER

Also known as: Correlative studies

Lapatinib and trastuzumab

pharmacological study OTHER

Also known as: Correlative studies

Lapatinib and trastuzumab

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (8)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

South Pasadena Cancer Center

Pasadena, California, 91030, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Lineberger Comprehensive Cancer Center, University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27704, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (5)

• 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.

  PMID: 16206252 BACKGROUND

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

  PMID: 17242669 BACKGROUND

• 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.

  PMID: 9111706 BACKGROUND

• 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.

  PMID: 15542812 BACKGROUND

• 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.

  PMID: 20124187 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Patient Compliance

Interventions

Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Daneng Li
• Organization: City of Hope

danli@coh.org

626-359-8111

Study Officials

• Daneng Li, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 10, 2011
• Study Start: April 20, 2011
• Primary Completion: February 22, 2018
• Study Completion (Estimated): May 19, 2026
• Last Updated: June 10, 2025
• Results First Posted: July 28, 2022

Record last verified: 2025-05

Locations

US (8)