An open-label, single-arm, multicentre, Phase II study of oral lapatinib in combination with paclitaxel as first-line treatment for ErbB2-amplified metastatic breast cancer patients - Phase II study of paclitaxel plus lapatinib in patients with ErbB2-amplified metastatic breast cance
- Conditions
- Metastatic breast cancer
- Registration Number
- EUCTR2005-003945-16-LV
- Lead Sponsor
- GlaxoSmithKline R&D Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 56
- Able to give signed informed consent
- Female, aged >=18years; if of child-bearing potential, the patient must have a negative serum pregnancy test and agree to use a protocol-defined acceptable method of birth control
- Histologically-confirmed Stage IV invasive breast cancer; where the disease is restricted to a solitary lesion, the neoplastic nature should be confirmed
- Patients with ER+ and/or PR+ disease or of unknown status will only be included if: they have symptomatic visceral disease requiring chemotherapy; the disease is rapidly progressing or life-threatening; the patient has received endocrine therapy but is no longer benefiting from this therapy
- Documented amplification of ErbB2 by FISH in primary or metastatic tumour tissue
- If prior taxane received in the adjuvant or neoadjuvant setting, disease progression must have occurred >=12months after completion of this treatment
- Measurable lesions according to RECIST
- Radiotherapy prior to start of study medication is allowed to a limited area if not the sole site of disease. Patients must have completed radiation treatment and recovered from all associated toxicities
- Bisphosphonate therapy for bone metastases is allowed provided this treatment was initiated before statrting study medication. Prophylactic bisphosphonate therapy is not permitted, except for osteoporosis.
- CNS metastases must be stable for at least 3months; patients with leptomeningeal involvement are only eligible if not taking oral steroids or enzyme-inducing anticonvulsants
- Patientys must have cardiac ejection fraction within the institutional range of normal by ECHO or MUGA. Patients with known history of uncontrolled or symptomatic angina, arrhythmias or CHF are not eligible.
- ECOG performance status 0-1
- Life expectancy >=3months
- Able to swallow and retain oral medication
- New or archived tumour tissue must be available for analysis
- Patients must complete all screening assessments per-protocol
- Patients must have adequate organ function as defined in the protocol.
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
- Pregnant or lactating
- Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy for metastatic disease
- Prior therapy with ErbB1 and/or ErbB2 inhibitors
- Concurrent anti-cancer therapy while taking study medication
- Unresolved or unstable, serious toxicity from prior administration of another IMP or cancer treatment
- >= Grade 2 peripheral neuropathy
- Malabsorption syndrome, disease significantly affecting GI function, or resection of stomach or small bowel. Patients with ulcerative colitis will be excluded.
- History of other malignancy (unless disease-free for >=5years, or history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma)
- Concurrent disease or condition that would make the patient inappropriate for participation in the study
- Active or uncontrolled infection
- Any condition that prohibits understanding or rendering of informed consent
- History of uncontrolled or symtomatic angina, arrhythmias or CHF
- Concurrent treatment with an IMP or participation in another clinical trial involving investigational agents
- Use of investigational drug within 30days or five half-lives, whichever is longer, prior to first dose of study medication
- Known hypersensitivity reaction or idiosyncracy to drugs chemically related to lapatinib or excipients, or related to paclitaxel or excipients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate overall tumour response rate (ORR) of lapatinib combined with paclitaxel in patients with ErbB2-amplified metastatic breast cancer;Secondary Objective: - To evaluate anti-tumour activity of lapatinib combined with paclitaxel in terms of: overall survival, duration of response, time to response, time to tumour progression (TTP), and progression-free survival (PFS)<br>- To determine the toxicities associated with treatment with lapatinib combined with paclitaxel<br>- To further characterise the patient population by determination of intra-tumoral biomarkers from archived tumour tissue; and by serum proteomic analysis<br>- To determine intra-tumoral genetic changes that may correlate with response to study treatment;Primary end point(s): Overall tumour response rate
- Secondary Outcome Measures
Name Time Method