E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-Positive Metastatic Breast Cancer (MBC) |
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E.1.1.1 | Medical condition in easily understood language |
HER2-Positive Metastatic Breast Cancer |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Progression-free survival (PFS) per investigator assessment
- Overall survival (OS) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the objective response rate (ORR) and landmark survival rate (6-month survival rate and 1-year survival rate) of trastuzumab emtansine compared with treatment of physician’s choice
• To evaluate the safety of trastuzumab emtansine compared with treatment of physician’s choice. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years
• Histologically or cytologically documented breast cancer
• Metastatic or unresectable locally advanced/recurrent breast cancer
• HER2-positive disease by prospective central laboratory confirmation
• Disease progression on the last systemic anti-cancer regimen received as defined by the investigator unless they were intolerant
• Prior treatment with trastuzumab, lapatinib, and a taxane in any setting
• Disease progression after at least two regimens of HER2 directed therapy in the metastatic or unresectable locally advanced/recurrent breast cancer
• A minimum of 6 weeks of prior trastuzumab
• Patients must have had at least 6 weeks prior exposure to lapatinib. |
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E.4 | Principal exclusion criteria |
• Chemotherapy ≤ 21 days before first study treatment
• Trastuzumab ≤ 21 days before first study treatment
• Lapatinib ≤ 14 days before first study treatment
• Prior enrollment in a trastuzumab emtansine−containing study, regardless of whether the patient received prior trastuzumab emtansine
• Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or corticosteroid therapy to control symptoms within 1 month of randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Progression-free survival by investigator assessment
• Overall survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• The primary PFS (by investigator assessment) analysis will be performed when approximately 324 PFS events have occurred, which is projected to be approximately 16 months from first patient enrolled in the trial (FPI).
• The first OS interim analysis will be performed at the time of the primary PFS analysis (approximately 16 months from FPI); the second interim analysis will be performed when approximately 67% of the targeted deaths (492) have occurred (approximately 26 months from FPI).
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E.5.2 | Secondary end point(s) |
• Objective response rate by investigator
• Duration of objective response
• Landmark survival rate. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After either PFS or OS (at any interim or final analysis) shows statistical significance, the secondary endpoints will be tested sequentially. |
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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 | 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 |
Overall survival (OS); progression-free survival, duration of response |
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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 | Yes |
E.8.1.6 | Cross over | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 88 |
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 |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Korea, Republic of |
Norway |
Poland |
Russian Federation |
Slovakia |
Spain |
Sweden |
Switzerland |
Thailand |
United Kingdom |
United States |
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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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The study will be considered completed when approximately 492 deaths have been reported (and the final analysis of OS is completed) or when the OS crosses the efficacy stopping boundary at either of the interim OS analyses. This is defined as the end of the study. |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |