E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 positive metastatic breast cancer which has progressed after one line of trastuzumab-based therapy in the metastatic setting. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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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 compare progression-free survival (PFS) between the two treatment arms based on assessments by an independent review facility (IRF). |
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E.2.2 | Secondary objectives of the trial |
- Overall survival (OS); - PFS based on tumor assessments by the Investigators; - Time to progression (TTP); - Time to treatment failure (TTF); - Overall objective response rate (ORR) clinical benefit rate (CBR), based on Investigator and IRF assessments; - Duration of objective response; - Safety and tolerability of trastuzumab plus capecitabine in combination with pertuzumab; - Correlation between biomarkers from tumor tissues and clinical outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease-Specific: 1. Pathologically confirmed breast cancer and documented metastatic disease. 2. HER2-positive (FISH/CISH-positive or IHC 3+) MBC confirmed by a Sponsor-designated central laboratory. Availability of a FFPE tumor tissue sample from primary tumor for eligibility testing (HER2-status) is mandatory (minimum 6 slides). Additional tumor tissue material for biomarker assessment is requested (if available). 3. Disease progression during or following a trastuzumab-based treatment for first-line metastatic breast cancer. 4. Trastuzumab must have been part of the last prior treatment regimen. 5. Prior treatment with a taxane-containing regimen. General: 6. Female patients, age ≥18 years. 7. LVEF ≥ 50% at baseline (assessed within 42 days prior to randomization) as determined by either 2D echocardiogram (ECHO) or MUGA (ECHO is the preferred method). If the patient is randomized, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study, and to the extent possible, be obtained at the same institution. 8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 9. For women of childbearing potential, agreement to use highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. For details see Section 7.2.6. 10. Written and signed informed consent (approved by the Independent Ethics Committee) obtained prior to beginning any protocol-specific procedures. |
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E.4 | Principal exclusion criteria |
Cancer-Related: 1. Prior therapy with pertuzumab or capecitabine; 2. Concurrent immunotherapy or anticancer hormonal therapy; 3. Existing acute reversible effects of prior treatment. This generally means at least 3 weeks should have elapsed since prior chemotherapy and at least 4 weeks since prior (radical) radiotherapy or major surgery; 4. History of another malignancy which could affect compliance with the protocol or interpretation of results. Patients treated with curative intent and disease-free for at least 5 years are generally eligible, as are patients treated curatively for carcinoma in situ of the cervix or non-melanomatous skin cancer; 5. CNS metastases which are not well controlled. Eligible patients must be asymptomatic, can not be receiving steroids, and must be enrolled at least 1 month after the end of the radiotherapy treatment. Note: CT or MRI scan of the brain is mandatory (within 4 weeks prior to randomization) in case of clinical suspicion of CNS metastases; 6. History of exposure to at least one of the following cumulative doses of anthracyclines: doxorubicin or liposomal doxorubicin > 360 mg/m2 epirubicin > 720 mg/m2 mitoxantrone > 120 mg/m2 idarubicin > 90 mg/m2 Other (e.g. liposomal doxorubicin or other anthracycline > the equivalent of 360 mg/m2 of doxorubicin) If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin. Hematological, Biochemical and Organ Function: 7. Current uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mmHg) or unstable angina; 8. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and/or paroxysmal supraventricular tachycardia); 9. History of myocardial infarction within 6 months of randomization; 10. History of LVEF decline to below 50% during or after prior trastuzumab therapy or other cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab; 11. Current dyspnoea at rest requiring supportive oxygen therapy or with significant pleural effusions. Et al... |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS based on IRF evaluation. PFS is defined as the time from randomization to the first documented radiographical progressive disease, as determined by IRF using RECIST version 1.0,1 or death from any cause, whichever occurs first. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 |
Valutazione di marcatori biologici |
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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) | 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 | 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.8.3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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 | Information not present in EudraCT |
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 |
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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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Lo studio terminera` con la morte o il ritiro dal follow up di sopravivenza del 90% delle pazienti o la conclusione della sperimentazione ad opera dello Sponsor. L`analisi OS finale avra` luogo al termine dello studio. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |