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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00105950
First received: March 18, 2005
Last updated: August 29, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Neoplasms, Breast
Drug: lapatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Objective Response rate (complete response plus partial response) [ Time Frame: Week 84 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical benefit (progression free survival, time to progression, response duration) [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR. [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression. [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment. [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: week 84 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Enrollment: 126
Study Start Date: March 2005
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib
Single arm study of lapatinib with no comparator arm.
Drug: lapatinib
Tyrosine kinase inhibitor administered daily at 1500 mg/kg
Other Name: lapatinib

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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:

  1. Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
  2. 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.

Exclusion criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105950

  Show 27 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Kaufman B, Wu Y, Amonkar M, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of Lapatinib Monotherapy on Quality of Life and Pain Symptoms in Patients With HER2+ Relapsed or Refractory Inflammatory Breast Cancer. [Curr Med Res Opin]. 2010;26(5):1065-1073.

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00105950     History of Changes
Obsolete Identifiers: NCT00214409, NCT00278317
Other Study ID Numbers: EGF103009
Study First Received: March 18, 2005
Last Updated: August 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
refractory inflammatory breast cancer
relapsed breast cancer
ErbB2 overexpressing
ErbB1 expressing

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014