E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER2 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 | 20.0 |
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 |
• To provide trastuzumab emtansine therapy as single agent trastuzumab emtansine or in combination with other agents to HER2- positive metastatic cancer patients who derived benefit from therapy administered in the Genentech/Roche-sponsored trastuzumab emtansine parent study. • To provide continued trastuzumab emtansine therapy as single agent trastuzumab emtansine or in combination with paclitaxel or with pertuzumab ± paclitaxel to HER2-positive metastatic cancer patients who derived benefit from therapy administered in the Genentech/Roche-sponsored trastuzumab emtansine parent study. • To provide continued study treatment to patients in the control arm of study BO21976/TDM4450g who derived benefit from the treatment administered during the study. • To collect safety data with regard to long-term administration of single agent trastuzumab emtansine or trastuzumab emtansine administered in combination with paclitaxel or in combination with pertuzumab ± paclitaxel. |
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E.2.2 | Secondary objectives of the trial |
not applicable - no secondary objectives |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Completed single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment in the parent study or who continue to receive single-agent trastuzumab emtansine or combination trastuzumab emtansine at the time of the parent study closure and received the last study drug dose within the 6 weeks (42 days) prior to the first dose of study therapy on the extension study or treatment in the control arm of study BO21976/TDM4450g at the time of the study closure. - Expectation by the investigator that the patient may continue to benefit from additional study treatment. - For women of childbearing potential, must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner during the treatment period and for at least 5 months after the final dose of atezolizumab (if applicable) or 7 months after the final dose of trastuzumab emtansine or pertuzumab, whichever is later. Women must refrain from donating eggs during this same period. For men, agreement to use an effective form of contraception and to continue its use for the duration of the study. Men must refrain from donating sperm during this same period. |
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E.4 | Principal exclusion criteria |
- Adverse events leading to single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment discontinuation in the parent study. - Ongoing serious adverse events from the parent study - Progressive disease (except for isolated CNS progression) on single-agent trastuzumab emtansine or a trastuzumab emtansine-containing regimen during the parent study or before starting the extension study. - Peripheral neuropathy of Grade >= 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0, v4.0 or v5.0, as utilized in the parent study - History of symptomatic congestive heart failure ([CHF]; New York Heart Association [NYHA] Classes II-IV), ventricular arrhythmia requiring treatment, or history of myocardial infarction within 6 months prior to study entry. - Severe dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy. - Current severe, uncontrolled systemic disease. - Major surgical procedure or significant traumatic injury within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment. - Current pregnancy or lactation. - History of receiving any investigational treatment or other systemic therapy directed at controlling cancer (i.e., chemotherapy, trastuzumab etc.) since the patient's last dose in the parent study. - History of hypersensitivity with previous trastuzumab emtansine or any agent used with trastuzumab emtansine in the parent study, precluding further dosing. - Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of adverse events leading to trastuzumab emtansine or combination treatment discontinuation or dose reduction. - Incidence of all adverse events and all serious adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Brazil |
Chile |
Israel |
Korea, Republic of |
Mexico |
Peru |
Taiwan |
United States |
Austria |
France |
Poland |
Bulgaria |
Spain |
Germany |
Italy |
Belgium |
Hungary |
Portugal |
Russian Federation |
United Kingdom |
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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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LVLS which will occur when the last patient on study treatment has progressed (except for isolated CNS progression), experiences unacceptable toxicity, or study closure. |
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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 | 10 |
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 | 15 |
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 |