E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ErbB2+ Metastatic Breast Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
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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 |
Primary Objective Open-label 'Safety Phase': To determine the safety and tolerability of lapatinib when administered in combination with both paclitaxel and trastuzumab.
Primary Objective Randomised Phase: To evaluate and compare time to progression (TTP) in women with ErbB2 amplified metastatic breast cancer treated with paclitaxel plus trastuzumab plus lapatinib to paclitaxel plus trastuzumab plus placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives Open-label 'Safety Phase': To determine the clinical activity of lapatinib when administered in combination with paclitaxel and trastuzumab.
Secondary Objectives Randomised Phase: To evaluate and compare the 2 treatment arms with respect to: overall survival, progression-free survival, overall response rate (complete or partial responses), clinical benefit, time to response, and duration of response. To determine the qualitative and quantitative toxicities associated with study treatments To evaluate the incidence of CNS progression To evaluate change in QoL status relative to baseline To evaluate plasma and tumour tissue biomarkers
Pharmacogenetics Research Objectives: To investigate the relationship between genetic variants in candidate genes in the host and response (efficacy, safety and tolerability) to the paclitaxel plus trastuzumab plus lapatinib combination.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed informed consent 2.Histologically confirmed invasive stage IV breast cancer 3.If adjuvant trastuzumab was administered, >=12 months must have elapsed since discontinuation 4.If a (neo)adjuvant taxane was administered, progression must have occurred >= 12 months after completion 5.Tumours that overexpress ErbB2 defined as either 3+ by IHC OR c-erbB2 gene amplification by FISH OR 0, 1+, 2+ by IHC and c-erbB2 gene amplification by FISH. 6.Patients must have tumour tissue available for central testing; 7.Measurable lesion(s) according to RECIST 8.Subjects must be females >= 18 years. •Non-childbearing potential or if of childbearing potential to follow a protocol-specific method of contraception 9.Radiotherapy is allowed if patients have completed treatment and recovered from all acute treatment-related toxicities 10.Bisphosphonate therapy is allowed if treatment was initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis; 11.ECOG Performance Status of 0 to 1; 12.For patients whose disease is ER+ and/or PR+ they should have visceral disease that requires chemotherapy or have rapidly progressing or life threatening disease or are no longer benefiting from hormonal therapy 13.Able to swallow and retain oral medication; 14.Cardiac ejection fraction within institutional range of normal 15.Adequate organ function |
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E.4 | Principal exclusion criteria |
1.Pregnant or lactating females; 2.Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization; 3.Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Patients with ulcerative colitis are also excluded; 4.History of other malignancy; however, patients who have been disease-free for five years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible; 5.Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety; 6.Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment; 7.Peripheral neuropathy of Grade 2 or greater; 8.Active or uncontrolled infection; 9.Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; 10.Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure; 11.Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis; 12.Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy); 13.Concurrent treatment with an investigational agent or participation in another clinical trial; 14.Concurrent treatment with any medication on the prohibited medications list 15.Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment; 16.Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting; 17.A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients; 18.A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients; 19.A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients; 20.Non compliance with any of the screening procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Initial safty phase is open-label; randomised phase is double-blind |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | Yes |
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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For data collection purposes, a patient will be considered as completing the study if the patient • has received investigational treatment (lapatinib or placebo) for 2 yrs • is no longer receiving treatment with investigational treatment and has completed 2 yrs of follow-up • has died prior to completing 2 yrs of study follow-up All pts should be followed for survival information until death when possible or until a maximum of 5 yrs after the last pt was enrolled, whichever comes first |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |