| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| women with ErbB2 overexpressing metastatic breast cancer who have received no more than one chemotherapeutic regimen in the metastatic setting. |
|
| 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 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 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 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate progression-free survival (PFS) in women with ErbB2-overexpressing MBC treated with lapatinib in combination with vinorelbine (Arm A) or lapatinib in combination with capecitabine (Arm B), who have received no more than 1 prior chemotherapeutic regimen in the metastatic setting. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the two treatment arms for the following: Overall response rate (ORR) [complete response (CR) and partial response (PR)] Overall survival (OS) Duration of response Time to response Clinical Benefit Rate (CBR) Qualitative and quantitative toxicities To characterize the PK of vinorelbine alone and in combination with lapatinib in a subgroup of subjects (at selected sites) receiving this combination |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Signed informed consent prior to registration. 2. Considered by the investigator to have a life expectancy of ≥12 weeks. 3. Subjects must be female and have histologically-confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease is restricted to a solitary lesion, the neoplastic nature of the lesion should be confirmed by cytology or histology. 4. Documented overexpression of ErbB2 by 3+ immunohistochemistry or a positive score by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridisation (CISH) using a local laboratory result on a specimen from the primary tumour or visceral metastatic site. Verification by a central laboratory is not required. 5. Subjects should have progressive disease following prior therapy which may include anthracyclines, taxanes, and trastuzumab. Subjects who have not received prior treatment for MBC must fulfill one or more of the following conditions: 1) Relapse following receipt of trastuzumab-based therapy in the adjuvant setting, 2) Contraindication to receiving trastuzumab or documented medical reason for trastuzumab not being appropriate 3) Unsuitable for taxane-based chemotherapy as determined by the study investigator. 6. All prior chemotherapy, immunotherapy, biologic therapy, or surgery (except for minor surgical procedures) must be discontinued or completed at least 4 weeks prior to first dose of randomized study medication. Hormonal therapy must be discontinued at least 1 week prior to first dose. Prior treatment with trastuzumab is permitted provided that at least 6 weeks has elapsed since the last dose of therapy and all treatment-related adverse events are  Grade 1 at the time of randomization. 7. Females aged ≥18 years with any menopausal status: Non-child-bearing potential Child-bearing potential with a negative serum pregnancy test at screening and agree to use acceptable methods of birth control 8. performance status (PS) of 0 to 1. 9. Subjects must have adequate organ and marrow function as defined in Table 3. 10. Subjects must have a cardiac ejection fraction of at least 50% and within the institutional range of normal. 11. Radiotherapy prior to initiation of study medication is allowed to a limited area (e.g., palliative therapy), if it is not the sole site of disease. 12. Subjects with stable central nervous system (CNS) metastases are permitted 13. Subject must be free of gastrointestinal diseases or any other conditions that impede swallowing, retaining, and absorption of oral medications. 14. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of study medication. |
|
| E.4 | Principal exclusion criteria |
| 1. Subjects taking medications listed in Section 5.9.2 are not eligible for the study. This includes human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib. 2. Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this study. 3. Prior therapy with more than one chemotherapeutic regimen for metastatic breast cancer. 4. Concurrent anticancer or concomitant radiotherapy treatment. 5. History of uncontrolled or symptomatic angina; history of arrhythmias requiring medications; clinically significant myocardial infarction <6 months from study entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below the institutional normal limit; or any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. 6. Have current active hepatic or biliary disease (with exception of patients with Gilbert`s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). 7. Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents. 8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients that in the opinion of the investigator or GSK Medical Monitor contraindicates their participation. 9. Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD). 10. Known history of uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subjects safety. 12. Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding). 13. Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication, including; malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, small bowel, or colon. Subjects with inflammatory bowel disease or ulcerative colitis are also excluded. 14. Peripheral neuropathy of Grade 2 or greater. 15. Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment. 16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy analysis will be based on PFS. PFS is the primary endpoint and is defined as the interval between the date of randomisation and the date of objective disesase progession or death from any cause. |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| 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 | 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 | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| lapatinib in combinaz con vinorelbina capecitabina |
|
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
| |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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