E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed infammatory breast cancer (IBC) |
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E.1.1.1 | Medical condition in easily understood language |
Newly diagnosed infammatory breast cancer (IBC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021974 |
E.1.2 | Term | Inflammatory breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of pathologic response rate following 14 days of neoadjuvant daily treatment with lapatinib monotherapy, followed by 12 weeks of daily lapatinib in combination with weekly-administered paclitaxel, in patients with treatment-naive IBC whose tumours overexpress ErbB2 +/- ErbB1 receptor(s) (Cohort A) and in patients whose tumours express the ErbB1 receptor but do not overexpress ErbB2 (Cohort B). |
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E.2.2 | Secondary objectives of the trial |
- To assess objective response rate following 14 days of lapatinib monotherapy and 12 weeks of lapatinib combined with weekly-administered paclitaxel - Assess safety and tolerability of once-daily lapatinib with weekly paclitaxel - Investigate pharmacodynamic effects of study treatment on intracellular biomarkers - Assess the effects of study treatment on proteomic profile and blood levels of extracellular domains of the ErbB1 and ErbB2 receptors - Pharmacogenetic investigation/s |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed breast carcinoma with clinical diagnosis of IBC - Tumour that:- Cohort A - overexpresses ErbB2 (defined IHC 2+ or 3+, or FISH-positive) with or without expression of ErbB1 (by IHC), or Cohort B - expression of ErbB1 (defined as IHC +) without overexpression of ErbB2. ErbB1 and ErbB2 status must be documented prior to dosing. - Tumour that is accessible for multiple biopsies - Male or female at least 18 years of age - Female patients must either be of non-childbearing potential, or if of childbearing potential to have negative serum pregnancy test at screening and to agree to a protocol-specified method of contraception during participation in the study - Able to swallow and retain oral medication - ECOG performance status 0-2 - Have adequate bone marrow function, and renal and hepatic function - Have left ventricular ejection fraction greater than or equal to 50% based on ECHO or MUGA scan - Provide written informed consent |
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E.4 | Principal exclusion criteria |
- Received prior biological, cytotoxic or hormonal therapy for breast cancer - Female who is pregnant or lactating - Patient who has malabsorption syndrome, disease affecting GI function, or resection of the stomach or small bowel - Considered medically unfit by the investigator - Has known hypersensitivity reaction or idiosyncrasy to drugs chemically-related to the IMPs - Received treatment with any investigational drug in previous 4 weeks - Currently receiving amiodarone or within 6 months prior to screening - Currently receiving oral steroid treatment, or any other protocol-specified prohibited medication. Use of cimetidine and/or steroids is permitted when required as standard treatment for paclitaxel administration. - Had major surgery within previous 2 weeks - Has condition/s which will not permit compliance with the protocol - Has peripheral neuropathy >= Grade 2 - Has Class II-IV heart failure (by NYHA classification system) - Has a clinically significant ECG abnormality - Has inadequate venous access for protocol-related blood sampling. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Determination of complete pathologic response rate (pCR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Information not present in EudraCT |
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E.5.2 | Secondary end point(s) |
Information not present in EudraCT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Information not present in EudraCT |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
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 |
Australia |
Belgium |
Canada |
France |
Israel |
New Zealand |
Spain |
Tunisia |
United Kingdom |
United States |
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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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Last subject, last visit. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |