E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
|
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 |
The primary objective of this study is to evaluate the efficacy of a daily dose of lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours with HER-2 or EGFR positive circulating tumour cells. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows: To evaluate antitumour activitiy of lapatinib To evaluate the safety of lapatinib To determine the early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA ALTRI SOTTOSTUDI: Positron Emission Tomography (PET) Sub-study
|
|
E.3 | Principal inclusion criteria |
1. Signed written informed consent 2. Female patients, age ≥ 18 years 3. Histologically confirmed diagnosis of HER-2 negative (i.e. no gene amplification by FISH or IHC 2+ and no amplification by FISH or IHC 0/1+) infiltrating primary breast cancer. UK centres will additionally require patients with EGFR positive primary breast cancer (i.e., IHC 3+ or FISH) 4. Evidence of HER-2 or EGFR positive circulating tumour cells (≥50% CTCs or FISH positive) in a peripheral blood sample taken at screening visit. 5. Metastatic disease with at least one measurable lesion as per RECIST criteria classification [Therasse, 2000] 6. No brain metastasis requiring local therapy. Stable or asymptomatic subjects are allowed. 7. Availability of tumour block or at least six unstained 4 µ sections of the primary tumour to be sent to the central lab after eligibility confirmation for HER-2 central testing by FISH. 8. Eastern Cooperative Oncology Group (ECOG) score for performance status 0 to 2 (Appendix 1) 9. Life expectancy > 12 weeks 10. Adequate baseline organ function at screening visit: Hematologic function: ANC ≥ 1,000 / mm3, PLT ≥ 50,000 / mm3 , Hb ≥ 9g / dL (after transfusion if needed) Hepatic function: GOT/GPT/alkaline phosphatase ≤ 3 N without liver metastases or ≤ 5 N if documented liver metastases; total bilirubin: ≤1.5 N unless due to Gilberts syndrome Renal function: serum creatinine ≤ 2.0mg/dL or Calculated Creatinine (Appendix 2) Clearance ≥ 25mL/min 11. Normal left ventricular ejection fraction (LVEF) by echocardiogram or MUGA. 12. Negative serum pregnancy test (only in childbearing potential female) 13. Patients with reproductive potential needs consistent and correct use of adequate non-hormonal methods of birth control (barrier methods or intrauterine device) 14. Previous treatment with anthracyclines and/or taxanes in the neo-adjuvant, adjuvant or advanced setting |
|
E.4 | Principal exclusion criteria |
1. Any unstable systemic disease including active infections, significant cardiovascular disease, as well as myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medication or that might affect the interpretation of the results or render the patient at high risk from treatment complications. 2. Pregnant or lactating women 3. Dementia, altered mental status, or any psychiatric condition that could prohibit the understanding or rendering of informed consent 4. Lack of physical integrity of the upper gastrointestinal (GI) tract, poor absorption of the GI tract or inability to take oral medication 5. Other co-existing malignancy or malignancies within the last 5 years with the exception of basal cell carcinoma or in-situ carcinoma 6. Concurrent anti-cancer therapies (chemo or hormonal therapy) other than study drug 7. Concurrent treatment with an investigational agent or participation in any investigational drug study within 4 weeks preceding treatment start 8. Concurrent radiotherapy to the only target lesion or concurrent bisphosphonates if bone metastases are the only target lesions 9. Previous treatment with anti HER-2 or anti-EGFR therapies 10. Protocol specified treatment regimens that would be inappropriate for the management of the subject |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the analysis is to evaluate the overall response rate (ORR) according to RECIST criteria. |
|
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) | 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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
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 | 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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |