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Neoplasms, BreastPhase 2NCT00105950

Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer

A Phase 2 study testing lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 27 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer. Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Breast
What is being tested?
lapatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
126 participants
Where
27 sitesin 8 countries
Study dates
Mar 2005to May 2010
Phase
Phase 2
Are there results?
None posted in the registry

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

Who may be able to join

  • Must have a life expectancy of at least 12 weeks.
  • Has a left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ lower limit of normal for the institution, based on ECHO or MUGA.
  • Aspartate and alanine transaminase (AST or ALT) ≤ 3 times the upper limit of the reference range (patients with liver metastases may have AST and ALT ≤ 5 times the upper limit of the reference range and may be enrolled).
  • Total bilirubin ≤ 3.0 mg/dL.
  • Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance (CrCl) ≥ 30 mL/min
  • Adequate bone marrow function. Hemoglobin ≥ 9 gm/dL. Absolute granulocyte count ≥ 1,500/mm³ (1.5 x 10^9/L). Platelets ≥ 75,000/mm³ (100 x 10^9/L).
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  • Recovered or stabilized sufficiently from side effects associated with previous chemotherapy, surgery or radiotherapy.
  • Provided written informed consent.
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
  • Able to swallow and retain oral medication.
  • Male or female, if female:
  • A female is eligible to enter and participate in the study if she is of:
  • Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
  • Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
  • Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period, and through the post-treatment follow-up visit (to occur 28 days after last dose of investigational product).
  • Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.
  • Implants of levonorgestrel. Injectable progestogen. Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
  • Oral contraceptives (either combined or progestogen only). Barrier methods including diaphragm or condom with a spermicide.
  • At least 18 years of age.
  • Has either measurable disease by Response Evaluation Criteria in Solid Tumors (RESIST) or clinically evaluable skin disease. Measurable lesions may be in the field of prior adjuvant irradiation; however, there must be at least an 8 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable.
  • Tumor that is accessible for biopsy.
  • Tumor that overexpresses ErbB2 defined as 3+ by IHC or FISH +. The ErbB 2 overexpression must be documented prior to dosing.
  • Documented disease progression or relapse following treatment, which must have contained a taxane and anthracycline-containing regimen in the adjuvant or metastatic setting (30 patients) plus trastuzumab (90 patients)
  • Histological diagnosis of breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.

Who cannot join

  • Is clinically assessed to have inadequate venous access for protocol-related blood draws.
  • Has a clinically significant electrocardiogram (ECG) abnormality.
  • Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Is currently receiving oral steroid treatment (inhaled steroids are permitted), or any other medication on the prohibited medications list
  • Is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
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  • Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
  • Has received treatment with any investigational drug in the previous 4 weeks.
  • Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product. These include other anilinoquinazolines, such as gefitinib [Iressa], erlotinib [Tarceva], or other chemically related compounds.
  • Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
  • Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. Patients with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants.
  • Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
  • Is a pregnant or lactating female.

Trial locations and contacts

27 sites in 8 countries.

27 sites in 8 countries

United States8 sites

  • GSK Investigational Site

    Bethesda, Maryland, 20892-1201

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Detroit, Michigan, 48201

  • GSK Investigational Site

    Durham, North Carolina, 27710

  • GSK Investigational Site

    Miami, Florida, 33136-1002

  • GSK Investigational Site

    Seattle, Washington, 98109

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    Zion, Illinois, 60099

Other trials in United States

France6 sites

  • GSK Investigational Site

    Bayonne, 64100

  • GSK Investigational Site

    Lyon, 69373

  • GSK Investigational Site

    Marseille, 13273

  • GSK Investigational Site

    Paris, 75248

  • GSK Investigational Site

    Paris, 75970

  • GSK Investigational Site

    Saint-Herblain, 44805

Other trials in France

Spain4 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Girona, 17007

  • GSK Investigational Site

    Madrid, 28041

Other trials in Spain

Tunisia4 sites

  • GSK Investigational Site

    Sfax, 3000

  • GSK Investigational Site

    Sfax, 3029

  • GSK Investigational Site

    Tunis, 1004

  • GSK Investigational Site

    Tunis, 1007

Other trials in Tunisia

Israel2 sites

  • GSK Investigational Site

    Ramat Gan, 52621

  • GSK Investigational Site

    Zrifin, 70300

Other trials in Israel

Belgium1 site

  • GSK Investigational Site

    Brussels, 1000

Other trials in Belgium

Canada1 site

  • GSK Investigational Site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

United Kingdom1 site

  • GSK Investigational Site

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer

This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer. Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry). Treatment will consist of daily oral therapy with lapatinib. A patient may continue treatment as long as they are receiving benefit. Blood samples for hematology and chemistry panels, MUGA/ECHO (multigated acquisition/echocardiogram) exams and physical exams will be performed throughout the study to monitor safety.

Read the detailed description

This Phase II open label, multicenter study is designed to evaluate the efficacy, safety, and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to patients with relapsed or refractory inflammatory breast cancer. Eligible patients must have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor that is readily accessible for biopsy, and must have previously received treatment with an anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients). Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of ErbB1. The primary objective for this study is to evaluate the objective response rate (defined as complete response plus partial response). Secondary objectives are to evaluate clinical benefit including quality of life parameters, progression-free survival, overall survival, time-to-response, response duration, safety and tolerability, pharmacodynamic effects on intracellular mediators that regulate tumor cell growth and survival, as well as effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and ErbB2 in peripheral blood.

Being tested
lapatinib
Keywords
ErbB2 overexpressing, ErbB1 expressing, relapsed breast cancer, refractory inflammatory breast cancer
Medical subject headings
Breast Neoplasms, Inflammatory Breast Neoplasms

What participants receive

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

  • lapatinibDrug

    Tyrosine kinase inhibitor administered daily at 1500 mg/kg

Study groups in NCT00105950
Study groupRoleWhat they receive
LapatinibExperimentalSingle arm study of lapatinib with no comparator arm.
Receives: Drug: lapatinib

What is being measured

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

  1. Objective Response rate (complete response plus partial response)

    Measured: Week 84

Secondary outcomes (10)

  1. Clinical benefit (progression free survival, time to progression, response duration)

    Measured: week 84

  2. Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months

    Measured: week 84

  3. Calculation of progression-free survival, defined as the time between the first dose of investigational product and the first documented sign of disease progression or death.

    Measured: week 84

  4. Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR.

    Measured: week 84

  5. Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression.

    Measured: week 84

  6. Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment.

    Measured: week 84

  7. Evaluation of adverse events (AEs), changes in laboratory values and echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) results from pre-dose, during dosing and post-dose assessments

    Measured: week 84

  8. Comparison of the effects of lapatinib on biomarkers that are involved in regulating tumor cell proliferation and survival (e.g., phosphorylated forms of Erk1/2 and Akt, STAT3, S6 Kinase, Bad, truncated ErbB2 and potentially other downstream mediators of

    Measured: Day 28

  9. tumor cell growth and survival) by quantitative IHC and by direct and genome-wide methods (e.g., direct sequencing and DNA microarray) in tumor tissue collected prior to and following 28 days of lapatinib monotherapy.

    Measured: Day 28

  10. Examination of the effects of lapatinib therapy on the levels of circulating ErbB1 and ErbB2 ECD and the proteomic profile of peripheral blood. Investigation of the use of FDG-PET to predict early response to treatment with lapatinib.

    Measured: Day 28

Timeline

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

  1. First posted21 Mar 2005 (estimated)
  2. Study startMar 2005
  3. Primary completionSep 2007
  4. Study completionMay 2010

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
126 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00105950
Sponsor's protocol ID
EGF103009
Status last verified
May 2015
First submitted
18 Mar 2005
Last updated
28 Sep 2015
Results posted
No
Data monitoring committee
No

Publications

  • Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, Johnston S. Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol. 2009 Jun;10(6):581-8. doi: 10.1016/S1470-2045(09)70087-7. Epub 2009 Apr 24.

    PubMed 19394894

  • Kaufman B, Wu Y, Amonkar MM, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of lapatinib monotherapy on QOL and pain symptoms in patients with HER2+ relapsed or refractory inflammatory breast cancer. Curr Med Res Opin. 2010 May;26(5):1065-73. doi: 10.1185/03007991003680323.

    PubMed 20214527

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 27 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, France, Spain, Tunisia, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response rate (complete response plus partial response) (time frame: Week 84). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00105950, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2015.

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