E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER-2 positive advanced breast cancer, locally unresectable or metastatic breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic, advanced 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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 | PT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
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 | PT |
E.1.2 | Classification code | 10006201 |
E.1.2 | Term | Breast cancer stage III |
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 | PT |
E.1.2 | Classification code | 10006202 |
E.1.2 | Term | Breast cancer stage IV |
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 | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | 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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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 |
Calculated average turn-around-time (TAT) time per patient per visit (per treatment cycle), measured with validated stop-watch in minutes for 8 cycles of the two different drug administration routes in the metastatic setting, time disaggregated per pre-specified task as well as per HCP (oncologist, nurse and pharmacist) measured by study nurses and coordinators. The calculation will be based on the different length of the three main subparts: Medical check-up, Pharmaceutical preparation and Drug administration. |
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E.2.2 | Secondary objectives of the trial |
The secondary effectiveness variables will focus on the longitudinal changes of TATs, and patient reported outcomes. I. Longitudinal evaluation of turn-around-time of treatments II. Assessment of patient reported outcomes: - Assessment of quality of life (EORTC QLQ C-30; EORTC QLQ BR-23) - Assessment of patient preference regarding the administration route (Patient Preference Questionnaire) - Assessment of therapy satisfaction and pain after each treatment cycle (Treatment satisfaction questionnaire (TASQ-SC and TASQ-IV); Subjective visual analogue pain assessment scale)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet the following criteria for study entry: -Have signed the informed consent -Age more than or equal with 18 years at time of signing Informed Consent Form; -Female patients with HER-2 positive advanced breast cancer, locally unresectable or metastatic breast cancer; -Ability to comply with the study protocol; -Eastern Cooperative Oncology Group (ECOG) Performance Status should be 0-1; -Good patient adherence; -Indication: histologically and by imaging confirmed HER-2 positive metastatic advanced breast cancer; -No contraindication of trastuzumab and pertuzumab treatment; -Finished preliminary combined chemotherapy cycles with pertuzumab and trastuzumab for breast cancer; -Life expectancy is more than 6 months; -Baseline LVEF is more than 50% measured by echocardiography (ECHO); -A negative serum pregnancy test for premenopausal female objects must be available prior to enrolment, unless they have undergone surgical sterilization (removal of ovaries and/or uterus).
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from study entry: -Having portacathether for intravenous administration; -Age above 75; -Early breast cancer (no confirmation of distant or local metastasis); -Progression to pertuzumab and trastuzumab treatments; -Severe cardiac co-morbidities (particularly patients with status of NYHA Class II-III-IV); -Pregnancy and/or breast feeding; -Severe psychiatric disorder; -Serious cardiac illness or medical conditions including, but not confined to, the following: High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate more than 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block);Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality; Angina pectoris requiring anti-anginal medication; Clinically significant valvular heart disease; Evidence of transmural infarction on ECG; Evidence of myocardial infarction within 12 months prior to starting neoadjuvant treatment; Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mmHg); History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalaemia, hypomagnesemia, hypocalcaemia), or family history of sudden unexplained death or long QT syndrome; EF is lower than 50%. -Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders); -Inadequate bone marrow function -Impaired liver function -Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis; -Concurrent, serious, uncontrolled infections, or known infection with human immunodeficiency virus (HIV); -Known hypersensitivity to study drugs, excipients, and/or murine proteins.
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E.5 End points |
E.5.1 | Primary end point(s) |
Null hypothesis (H_0): There is no difference between the average total turn-around-times (TAT) of the subcutaneously and intravenously routed pertuzumab and trastuzumab. Alternative hypothesis (H_1): Average total TAT of the fixed dose combination of pertuzumab-trastuzumab study arm is shorter compared that of the intravenous pertuzumab-trastuzumab study arm.
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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) |
Longitudinal analysis of the changes of total and subpart TATs H_0: Neither the total nor the subpart TATs change in time with the course of the study. H_1: Either the total or the subpart TATs change in time with the course of the study.
Do the EORTC QLQ-C30 scores differ between the two study arms? H_0: There is no difference in the EORTC QLQ-C30 scores between the two study arms. H_1: The EORTC QLQ-C30 scores differ between the two study arms.
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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 | No |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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) | 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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Last visit of the last subject |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |