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

NCT00105950 | Completed Phase 2

• 1 other identifier: EGF103009
• Study Type: interventional
• Target: 126
• Locations: 8 countries
• Sites: 27

Brief 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). 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.

Conditions

Neoplasms, Breast

Keywords

ErbB2 overexpressing; ErbB1 expressing; relapsed breast cancer; refractory inflammatory breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response rate (complete response plus partial response)

  Week 84

Secondary Outcomes (10)

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

  week 84

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

  week 84

• 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.

  week 84

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

  week 84

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

  week 84

Study Arms (1)

Lapatinib

EXPERIMENTAL

Single arm study of lapatinib with no comparator arm.

Drug: lapatinib

Interventions

lapatinib DRUG

Tyrosine kinase inhibitor administered daily at 1500 mg/kg

Lapatinib

Eligibility Criteria

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

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (27)

GSK Investigational Site

Miami, Florida, 33136-1002, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Zion, Illinois, 60099, United States

Location

GSK Investigational Site

Bethesda, Maryland, 20892-1201, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Bayonne, 64100, France

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Marseille, 13273, France

Location

GSK Investigational Site

Paris, 75248, France

Location

GSK Investigational Site

Paris, 75970, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Ramat Gan, 52621, Israel

Location

GSK Investigational Site

Zrifin, 70300, Israel

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Girona, 17007, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Sfax, 3000, Tunisia

Location

GSK Investigational Site

Sfax, 3029, Tunisia

Location

GSK Investigational Site

Tunis, 1004, Tunisia

Location

GSK Investigational Site

Tunis, 1007, Tunisia

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 19394894 RESULT

• 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.

  PMID: 20214527 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2005
• First Posted: March 21, 2005
• Study Start: March 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: May 1, 2010
• Last Updated: September 28, 2015

Record last verified: 2015-05

Locations

FR (6); TU (4); US (8); GB (1); CA (1); ES (4); IL (2); BE (1)