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 | 14.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 | 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 |
- Objective response rate by independent review - Overall survival (OS) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the objective response rate (ORR) by investigator assessment • To evaluate the progression-free survival, duration of response, clinical benefit rate, and landmark survival rate (6-month survival rate and 1-year survival rate) of T-DM1 compared with treatment of physician’s choice • To evaluate the safety of T-DM1 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 regimen received as defined by the investigator • Prior treatment with an anthracycline, trastuzumab, a taxane,lapatinib, and capecitabine • Disease progression after at least 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 prior exposure to lapatinib and capecitabine. |
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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 T-DM1−containing study, regardless of whether the patient received prior T-DM1 • Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms within 2 months of randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective response rate by independent review • Overall survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Final analysis of OS will take place about 36 months after FPI.
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E.5.2 | Secondary end point(s) |
• Objective response rate by investigator • Progression-free survival (PFS) • Duration of objective response • Clinical benefit rate • Landmark survival rate. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Analysis will take place when 489 patients enrolled and followed for 9 months i.e. about 30 months from FPI.
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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, clinical benefit rate |
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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 | 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) | 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 | 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 | 3 |
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 |
Austria |
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 date of data cutoff for primary analysis of objective response rate (ORR) will be approximately 9 months after approximately 489 patients with measurable disease at baseline (as determined by IRF) have been enrolled. The final analysis of Overall Survival (OS) data cutoff will be after approximately 496 deaths have occurred. The study will be closed following the final analysis of OS. |
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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 | 2 |
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 |