E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic breast cancer over expressing HER2 and ≥ 70 years old |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048406 |
E.1.2 | Term | Breast cancer aggravated |
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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 |
To assess clinical benefit (defined at 4 months as complete response, partial response or stable disease), safety and preserved geriatric independence. (main objective is a “bi-criteria” or composite criteria). |
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E.2.2 | Secondary objectives of the trial |
- Duration of clinical benefit - Time to progression defined as the time from inclusion to disease progression or death due to breast cancer - Overall response rate - Progression free survival (the time from inclusion to disease progression or death due to any cause) - Overall survival - Time to treatment failure - Determination of toxicity of the combination - Number of patients treated with 3 and 6 cycles and % of dose administrated - Investigation of the minimal and maximal concentration (Cmin-Cmax) of lapatinib and capecitabine - Geriatric impact of the combination on ADL, IADL, G8 (ONCODAGE) , QLQC30 item 29-30 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 70 2. Histological confirmed advanced breast cancer (metastatic or locally advanced) 3. Tumor over expressing HER2 (HER2 3+ in IHC or IHC 2+ and Fish positive) in sample from the primary and/or secondary tumor 4. WHO performance status (EGOG) from 0 to 2 5. MMS > 25 6. Measurable disease (RECIST criteria) 7. Progression of disease after one metastatic line of chemotherapy associated with trastuzumab (must be stopped at least 3 weeks before beginning the trial) 8. Adequate hematological function (Hb ≥ 9g/dl, ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3) 9. Adequate hepatic function (total bilirubine ≤ 2.5 mg/dl, ASAT and ALAT ≤ 3ULN) 10. Adequate renal function (measured or calculated creatinine clearance ≥ 40 ml/min - Cockroft) 11. LVEF ≥ 50% (US or isotopic method) 12. Absence of treatment by enzymatic inhibitors or inducers or any gastric pH modifying agent/drug within a 7-to-14 day period preceding the first administration of one of the trial’s products and within the overall duration of the study (see medication list) 13. Patients must be affiliated to a Social Security System 14. Patient information and written informed consent form signed |
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E.4 | Principal exclusion criteria |
1. Life expectancy < 3 months 2. Prior treatment with capecitabine or lapatinib 3. Concomitant radiotherapy except for palliative reason and more than 25% of the BM 4. Patients with pre-existing toxicity ≥ grade 2 (excepted alopecia) 5. Patients with dysphagia, or inability to swallow the capsules. 6. Patient with malabsorption syndrome or disease significantly affecting gastro-intestinal function or with major resection of stomach or proximal bowel that could affect absorption of oral drugs 7. Patient already included in another therapeutic trial using an experimental drug within 30 days preceding entry into the study 8. Individual deprived of liberty or placed under the authority of a tutor 9. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
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E.5 End points |
E.5.1 | Primary end point(s) |
The trial is designed according to the Bryant and Day methodology, allowing the evaluation of both (1) therapeutic efficacy and (2) tolerance, this latter encompassing standard toxicity due to treatment (NCIC CTC v.4) and deleterious impact of treatment on functional status (IADL). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 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) | 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 | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |