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Breast NeoplasmsPhase 2NCT01273610

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

A Phase 2 study testing Lapatinib, Trastuzumab and laboratory biomarker analysis in people with Breast Neoplasms and HER2/Neu Positive, run by City of Hope Medical Center at 8 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Lapatinib, Trastuzumab and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesUnited States
Study dates
20 Apr 2011to 20 Apr 2027
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Lineberger Comprehensive Cancer Center, University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • City of Hope Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27704

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • South Pasadena Cancer Center

    Pasadena, California, 91030

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

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.

Read the 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.

Being tested
Lapatinib, Trastuzumab, laboratory biomarker analysis, pharmacological study
Keywords
Breast Neoplasms, HER2 protein, human, Geriatric Health Services, Antineoplastic Agents, Combined, Geriatric Assessment, Pharmacokinetics, Toxicity, Patient Adherence
Medical subject headings
Breast Neoplasms, Patient Compliance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

    Also called Tykerb, Tyverb, GSK572016, GW-572016

    250 mg tablets

  • TrastuzumabDrug

    Also called Herceptin

    Intravenous injection

  • laboratory biomarker analysisOther

    Also called Correlative studies

  • pharmacological studyOther

    Also called Correlative studies

Study groups in NCT01273610
Study groupRoleWhat they receive
Lapatinib and trastuzumabExperimentalPatients 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.
Receives: Drug: Lapatinib; Drug: Trastuzumab; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. 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.

    Measured: While on treatment, up to 4.5 years

  2. 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.

    Measured: While on treatment, up to 4.5 years

  3. 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.

    Measured: 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.

  4. Median Overall Survival (OS)

    OS will be estimated using the product limit method of Kaplan and Meier across all ages per protocol plan.

    Measured: Time from start of treatment to death due to any cause, with average follow up of 4.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2011 (estimated)
  2. Study start20 Apr 2011
  3. Primary completion22 Feb 2018
  4. Study completion20 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01273610
Sponsor's protocol ID
10112
Other IDs
NCI-2011-00116
Status last verified
Jun 2026
First submitted
6 Jan 2011
Last updated
25 Jun 2026
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 16206252

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

    PubMed 17242669

  • 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.

    PubMed 9111706

  • 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.

    PubMed 15542812

  • 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.

    PubMed 20124187

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