E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-positive primary breast cancer. |
|
E.1.1.1 | Medical condition in easily understood language |
HER2-positive primary breast cancer. |
|
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 | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 compare invasive disease-free survival (IDFS) in patients with residual invasive breast cancer after treatment with preoperative chemotherapy and HER2-directed therapy including trastuzumab followed by surgery between the 2 treatment arms |
|
E.2.2 | Secondary objectives of the trial |
- To compare IDFS including second non-breast cancers, disease-free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI) between the 2 treatment arms.
- To compare side effects of the study medication between the 2 treatment arms. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult patients, aged at least 18 years
• Histologically confirmed invasive breast cancer with clinical staging T1-4, N0-3, M0 (no metastasis)
• HER2-positive tumor as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
• Patients must have received at least 6 cycles with 16 weeks of prior chemotherapy in the preoperative (neoadjuvant) setting including at least 9 weeks of a taxane and 9 weeks of HER2-directed therapy which may be given concurrently
• Surgical removal of all clinically-evident disease in the breast and lymph nodes
• Pathologic evidence of residual invasive cancer following completion of preoperative chemotherapy
• ECOG performance status of 0 or 1
• Life expectancy of at least 6 months from the first dose of study treatment
• Adequate organ function as determined by the following laboratory results, within 14 days prior to randomization. |
|
E.4 | Principal exclusion criteria |
• Metastatic breast cancer
• History of any prior breast cancer except for lobular carcinoma in situ
• Treatment with a cumulative dose of epirubicin greater than 480mg/m2 or any other anthracycline like doxirubicin greater than 240mg/m2
• Treatment with any investigational anticancer drug within 28 days prior to commencing study treatment
• History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
• Peripheral neuropathy greater or equal to Grade 2
• Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, angina, serious cardiac arrhythmia)
• Myocardial infarction within 12 months prior to randomization
• Active liver disease like hepatitis
• Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
• For female patients, current pregnancy or lactation
• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• Currrent, serious, uncontrolled Infections or known infection with HIV. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Invasive disease-free survival (IDFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. IDFS including second non-breast cancer
2. Disease-free survival (DFS), including second non-breast cancer or contralateral or ipsilateral ductal carcinoma in situ
3. Overall survival (OS)
4. Recurrence-free interval (RFI): time between randomization and local, regional or distant breast cancer recurrence
5. Distant recurrence-free interval (DRFI): time between randomization and distant breast cancer recurrence
6. Cardiac and overall safety: Incidence of adverse events
7. Quality of life: EORTC QLQ-C30, QLQ-BR23 and EQ-5D questionnaires. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 6. up to 13 years
7. up to 3 years
|
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | 2 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
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 |
Argentina |
Austria |
Belgium |
Brazil |
Canada |
China |
Colombia |
Czech Republic |
France |
Germany |
Greece |
Hong Kong |
Ireland |
Israel |
Italy |
Mexico |
Panama |
Peru |
Russian Federation |
Serbia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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
|
The study will end after the last patient randomized into the study has undergone the last follow-up assessment. To enable long-term follow-up for survival and safety information, the last follow-up assessment is scheduled to occur 10 years after the first patient is randomized. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |