E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 positive Metastatic Breast Cancer patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 the antitumor activity of XRP9881 in combination with trastuzumab as assessed by objective response rate (RR) observed during the study period (lasting up to 6 months after the last patient is enrolled) |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability of XRP9881 in combination with trastuzumab - To assess any pharmacokinetic interaction of XRP9881 and trastuzumab when given in combination - To evaluate the progression-free survival (PFS), brain metastasis progression, and overall survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically proven diagnosis of breast adenocarcinoma that is now metastatic or locally recurrent and inoperable for curative intent. - Tumor (primary or metastatic) must show the presence of the HER2 gene amplification by fluorescence in situ hybridation (FISH analysis) or 3+ on the immunohistochemistry assay (IHC). - Prior treatment with trastuzumab, in neo-adjuvant , adjuvant or metastatic setting is allowed provided that no more than one progression under trastuzumab based regimen has been reported. - Patients may have received an anthracycline and/or a taxane (paclitaxel or docetaxel) prior to entry in the protocol provided the dose of anthracycline doesn’t exceed the total cumulative dose of 360 mg/m² of doxorubicin or 750 mg/m² of epirubicin, due to potential increased risk of cardiotoxicity with trastuzumab. - Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST). - Asymptomatic brain metastases are allowed (systematic brain CT-scan is mandatory at baseline), provided they were not pre-irradiated.
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E.4 | Principal exclusion criteria |
- History of hypersensitivity grade ≥3 to taxanes, Polysorbate-80, or to compounds with similar chemical structures. - Cardiac dysfunction with LVEF (echocardiography or MUGA scan) < 50% (due to an increased risk of cardiac toxicity with trastuzumab). The LVEF evaluation should have been performed within one month prior registration. - History of hypersensitivity grade ≥ 3 to trastuzumab. - More than one previous chemotherapy regimen for metastatic disease. - The following breast cancer treatments are not allowed : XRP9881 or any taxane-analogs except for paclitaxel or docetaxel (e.g., epothilones , Abraxane® or experimental preparations of paclitaxel), Anti-oestrogen therapy, Prior treatment with other HER2 antagonist than trastuzumab. - Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to registration. - Any of the following within the 6 months prior to registration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (grade 3-4). - History of inflammatory bowel disease or chronic diarrhea. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the objective response that is defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the study period, as defined by the RECIST criteria. |
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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 | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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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The duration of this study planned to take approximately 18 months was finally longer, including 21 months for patients accrual and 6 months follow-up in order to assess median Progression Free Survival for the whole population. The study cut-off date has been achieved 6 months after the last enrolled patient but the end of trial is until disease progression, unacceptable toxicity, consent withdrawn or physician decision. |
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |