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Phase II study to evaluate the efficacy, safety and pharmacodynamics of lapatinib in patients with relapsed or refractory inflammatory breast cancer.

Phase 1
Conditions
Relapsed or refractory infammatory breast cancer (IBC)
MedDRA version: 14.1Level: LLTClassification code 10021974Term: Inflammatory breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2004-001906-29-ES
Lead Sponsor
GlaxoSmithKline R&D Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
0
Inclusion Criteria

- Histologically confirmed breast carcinoma with clinical diagnosis of IBC
- Documented disease progression or relapse following treatment, which must have included a taxane and anthracycline-containing regimen in the adjuvant or metastatic setting (30 patients) plus trastuzumab (90 patinets)
- Tumour that overexpresses ErbB2 as 3+ by IHC or FISH-positive. The ErbB2 expression status must be documented prior to dosing.
- Tumor that has negative estrogen and progesterone receptor status utilizing biopsy tissue obtained within 60 days of screening.
- Must have life expectancy of at least 12 weeks
- Tumour to be accessible for biopsy
- Measureable disease by RECIST or clinically evaluable skin disease
- Male or female at least 18 years of age
- Female patients must either be of non-childbearing potential, or if of childbearing potential to have negative serum pregnancy test at screening and to agree to a protocol-specified method of contraception during participation in the study
- Able to swallow and retain oral medication
- ECOG performance status 0-2
- Recovered or stabilised from effects of previous chemotherapy, surgery or radiotherapy
- Have adequate bone marrow function, and renal and hepatic function
- Have left ventricular ejection fraction greater than or equal to 50%, or above lower limit of normal for the institution
- Provide written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

- Female who is pregnant or lactating
- Patient who has malabsorption syndrome, disease affecting GI function, or resection of the stomach or small bowel
- 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.
- Considered medically unfit by the investigator
- Has known hypersensitivity reaction or idiosyncrasy to drugs chemically-related to the IMP
- Received treatment with any investigational drug in previous 4 weeks
- Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days (except mitomycin C within past 6 weeks)
- Currently receiving amiodarone or within 6 months prior to screening
- Currently receiving oral steroid treatment, or any other protocol-specified prohibited medication
- Has condition/s which will not permit compliance with the protocol
- Has Class II-IV heart failure (by NYHA classification system)
- Has a clinically significant ECG abnormality
- Has inadequate venous access for protocol-related blood sampling.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Evaluation of objective response rate (complete response + partial response) to lapatinib treatment in patients with relapsed or refractory IBC whose tumours overexpress ErbB2;Primary end point(s): Assessment of Objective Response Rate (defined as Complete Response plus Partial Response);Timepoint(s) of evaluation of this end point: .;Secondary Objective: - Evaluate other measures of anti-tumour activity<br>- Assess safety and tolerability of study treatment<br>- Investigate pharmacodynamic effects of study treatment on intracellular biomarkers<br>- Assess the effects of study treatment on proteomic profile and blood levels of extracellular domains of the ErbB1 and ErbB2 receptors<br>- To examine use of FDG-PET as an early predictor of response to study treatment<br>- Pharmacogenetic investigation/s
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): .;Timepoint(s) of evaluation of this end point: .
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