E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate overall tumour response rate (ORR) of lapatinib combined with paclitaxel in patients with ErbB2-amplified metastatic breast cancer |
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E.2.2 | Secondary objectives of the trial |
- 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) - To determine the toxicities associated with treatment with lapatinib combined with paclitaxel - To further characterise the patient population by determination of intra-tumoral biomarkers from archived tumour tissue; and by serum proteomic analysis - To determine intra-tumoral genetic changes that may correlate with response to study treatment |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- 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. |
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E.4 | Principal exclusion criteria |
- 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall tumour response rate |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |