E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ErbB2 Overexpressing Locally Advanced or Metastatic Breast Cancer |
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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 offer pre-approval access to lapatinib, in combination with capecitabine, in order to provide potential clinical benefit to subjects with ErbB2 overexpressing breast cancer, who have previously received anthracyclines, taxanes and trastuzumab, and who are not eligible for another ongoing lapatinib clinical trial. |
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E.2.2 | Secondary objectives of the trial |
- To characterize progression-free survival and overall survival of subjects treated with lapatinib in combination with capecitabine.
- To evaluate the serious adverse events (SAEs) associated with this combination therapy in this population of patients with locally advanced or metastatic breast cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent;
2. Subjects must not be eligible for another ongoing lapatinib clinical study;
3. Subjects must NOT have received prior lapatinib therapy in another clinical study; however, previous capecitabine therapy is permitted;
4. Prior treatment with hormonal therapy is allowed;
5. Subjects must have advanced or metastatic breast cancer with progression (as assessed by RECIST) after prior therapy which must include ALL of the following: prior treatment with an anthracycline, a taxane and trastuzumab alone or in combination with other chemotherapy. Trastuzumab administered in the adjuvant setting is not exclusionary, but for eligibility, trastuzumab must also have been administered in the locally advanced or metastatic setting;
6. Subjects must have tumours that overexpress ErbB2 defined as 3+ by IHC or FISH positive for ErbB2 gene amplification. The status of ErbB2 expression must be documented prior to study entry;
7. Subjects (male or female) must be ≥ 18 years of age;
8. Subjects must have an ECOG Performance Status of 0 to 2;
9. Life expectancy > 8 weeks;
10. Subjects must have recovered or stabilized sufficiently from side effects associated with prior treatments before beginning treatment with lapatinib and capecitabine;
11. Subjects with central nervous system (CNS) metastases are eligible, providing treatment with prohibited medications are not required;
12. Cardiac ejection fraction within the institutional range or normal as measured by echocardiogram (ECHO). Measurements with MUGA scans are allowed if echocardiograms cannot be performed. Subjects with symptomatic angina, arrhythmias, or congestive heart failure are not eligible;
13. Subjects must not be taking any medication listed in the 'Prohibited Medications' listing of the protocol;
14. Able to swallow and retain oral medications;
15. Subjects must complete all screening assessments as outlined in the protocol;
16. Subjects must have adequate hematologic, hepatic and renal function as defined in the protocol. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating females at anytime during the study;
2. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded;
3. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety;
4. Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
5. Uncontrolled infection;
6. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
7. Active cardiac disease, defined as one or more of the following:
- History of uncontrolled or symptomatic angina - History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation - Myocardial infarction < 6 months from study entry - Uncontrolled or symptomatic congestive heart failure - Ejection fraction below the institutional normal limit - Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
8. Subjects receiving concurrent chemotherapy (other than capecitabine), radiation therapy, immunotherapy, biologic therapy (including ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer. Hormone therapy for ovarian supression is allowed. Concurrent treatment with bisphosphonates is allowed;
9. History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib or to any excipients;
10. History of allergic reactions attributed to compounds of similar chemical composition to capecitabine, fluorouracil or to any excipients;
11. Known dihydropyrimidine dehydrogenase (DPD) deficiency. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression Free Survival (PFS)
2. Overall survival (OS) |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 215 |
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 | 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
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |