A Phase II study to evaluate the efficacy, safety and pharmacodynamics of lapatinib in combination with paclitaxel as neoadjuvant therapy in patients with newly diagnosed inflammatory breast cancer - Lapatinib combined with paclitaxel in newly diagnosed inflammatory breast cancer (IBC)
- Conditions
- ewly diagnosed infammatory breast cancer (IBC)
- Registration Number
- EUCTR2004-001905-93-GB
- Lead Sponsor
- GlaxoSmithKline R&D Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
- Histologically confirmed breast carcinoma with clinical diagnosis of IBC
- Tumour that:-
Cohort A - overexpresses ErbB2 (defined IHC 2+ or 3+, or FISH-positive) with or without expression of ErbB1 (by IHC), or
Cohort B - expression of ErbB1 (defined as IHC +) without overexpression of ErbB2.
ErbB1 and ErbB2 status must be documented prior to dosing.
- Tumour that is accessible for multiple biopsies
- 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
- Have adequate bone marrow function, and renal and hepatic function
- Have left ventricular ejection fraction greater than or equal to 50% based on ECHO or MUGA scan
- 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
- Received prior biological, cytotoxic or hormonal therapy for breast cancer
- Female who is pregnant or lactating
- Patient who has malabsorption syndrome, disease affecting GI function, or resection of the stomach or small bowel
- Considered medically unfit by the investigator
- Has known hypersensitivity reaction or idiosyncrasy to drugs chemically-related to the IMPs
- Received treatment with any investigational drug in previous 4 weeks
- Currently receiving amiodarone or within 6 months prior to screening
- Currently receiving oral steroid treatment, or any other protocol-specified prohibited medication. Use of cimetidine and/or steroids is permitted when required as standard treatment for paclitaxel administration.
- Had major surgery within previous 2 weeks
- Has condition/s which will not permit compliance with the protocol
- Has peripheral neuropathy >= Grade 2
- 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
Name Time Method Main Objective: Evaluation of pathologic response rate following 14 days of neoadjuvant daily treatment with lapatinib monotherapy, followed by 12 weeks of daily lapatinib in combination with weekly-administered paclitaxel, in patients with treatment-naive IBC whose tumours overexpress ErbB2 +/- ErbB1 receptor(s) (Cohort A) and in patients whose tumours express the ErbB1 receptor but do not overexpress ErbB2 (Cohort B).;Secondary Objective: - To assess objective response rate following 14 days of lapatinib monotherapy and 12 weeks of lapatinib combined with weekly-administered paclitaxel<br>- Assess safety and tolerability of once-daily lapatinib with weekly paclitaxel<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>- Pharmacogenetic investigation/s;Primary end point(s): Determination of complete pathologic response rate (pCR)
- Secondary Outcome Measures
Name Time Method