E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic breast cancer |
Carcinoma mammario metastatico
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer with metastases |
Tumore mammario con presenza di metastasi
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006285 |
E.1.2 | Term | Breast neoplasm NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 in the experimental group compared to standard chemotherapy |
Comparazione della sopravvivenza libera da progressione (PFS) nel braccio sperimentale vs braccio di controllo |
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E.2.2 | Secondary objectives of the trial |
- To compare overall survival - To compare response rates - To evaluate safety of the strategy as a whole - To explore the efficacy (response rate, progression-free survival, overall survival) of the individual targeted agents. - To correlate molecular mechanisms in patients with the efficacy endpoints (response rate, progression-free and overall survival) - To investigate the additional molecular mechanisms in patients with tumor response versus patients without tumor response.
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- Comparazione della sopravvivenza globale (OS) - Comparazione del tasso di risposta - Valutazione della sicurezza e della fattibilità della strategia diagnostico-terapeutica - Valutazione esplorativa dell'efficacia e della sicurezza dei singoli farmaci sperimentali - Correlazione delle alterazioni molecolari con gli endpoint di efficacia e tossicità - Valutazione della sensibilità della detezione di mutazioni nel DNA circolante come predittore di - progressione di malattia e resistenza molecolare
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Screening 1. Provision of signed, written and dated informed consent for genetic research. 2. Patients with histologically confirmed breast adenocarcinoma. 3. Patient has radiologic evidence of inoperable locally advanced, or metastatic BC 4. Presence of an accessible metastatic lesion for biopsy or at least one archived metastatic tumour sample collected no longer than 6 months earlier. 5. Presence of measurable target lesion according to RECIST criteria v1.1. 6. Age > 18 years and <75 years. 7. PS 0/1 8. Patient must have received a minimum of 1 line of chemotherapy and\or endocrine therapies in the metastatic setting. Patients with HER2+ disease must have received 3 or more line of antiHER2 treatment (including dual blockade with pertuzumab/trastuzumab if reimbursed, TDM1 and lapatinib). 9. Life expectancy =3 months. 10. For women with childbearing potential, a negative pregnancy test within 14 days prior to initiation of the study drug. 11. Ability to swallow oral capsules 12. Normal echocardiogram at baseline (left ventricular ejection fraction [LVEF] >50% and shortening fraction [SF] >15%).
PATIENT RANDOMIZATION IN THE THERAPEUTIC PHASE Inclusion criteria: 1) Patients who still meet the screening phase inclusion criteria 2) Patients will have had a minimum of 21 days gap from last chemotherapy or biological therapy administration prior to therapy modification.
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Allo screening: 1. Firma del consenso informato per la ricerca genetica 2. Pazienti con tumore metastatico della mammella confermato istologicamente 3. Pazienti con evidenza di tumore inoperabile della mammella, metastatico o avanzato 4. Altra sede accessibile a biopsia, oppure presenza di materiale di archivio non più vecchio di 6 mesi 5. Presenza di malattia misurabile secondo i criteri RECIST V1.1 6. Età > 18 anni e < 75 anni 7. PS 0/1 8. Pazienti devono aver ricevuto almeno 1 linea di chemioterapia e/o endocrinoterapia nel setting metastatico. Pazienti HER2+ devono aver ricevueto 3 o più linee di terapia anti HER2 (inclusi pertuzumab/trastuzumab, TDM1 e lapatinib) 9. Aspettativa di vita =3 mesi 10. Test di gravidanza negative (per le donne in età fertile) 11. Capacità di assumere farmaco orale 12. Ecocardiogramma normale al baseline ( LVEF >50% e SF >15%)
PAZIENTI RANDOMIZZATI NELLA FASE TERAPEUTICA Inclusion criteria: 1) Pazienti devono soddisfare i criteri precedent 2) pazienti devono avere uno stop di almeno 21 giorni dall’ultima chemioterapia o ultima terapia biologica |
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E.4 | Principal exclusion criteria |
1. Patients with known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anti-convulsant medications for at least 2 weeks prior to the first dose of study medication. 2. History of clinically significant or uncontrolled cardiac disease, including angina, coronary artery bypass graft, angioplasty, vascular stent , myocardial infarction, atrial fibrillation within 6 months or history of ventricular arrhythmia, Congestive Cardiac Failure (CCF) or Ischaemic Heart Disease (IHD) with no limit of time (New York Heart Association [NYHA] functional classification = 3. Uncontrolled arterial hypertension (defined as systolic blood pressure = 140mmHg and/or diastolic blood pressure = 90mmHg with optimized antihypertensive therapy or patient treated with more than 2 antihypertensive agents) or systolic blood pressure = 160mmHg and/or diastolic blood pressure = 100mmHg : 4. Participation in another clinical study with an investigational product (IP) during the last 30 days. 5. Bone metastases as the only site of biopsiable disease 6. Previous treatment with the study drugs or drugs of this class (e.g. Everolimus)
PATIENT RANDOMIZATION IN THE THERAPEUTIC PHASE 1) Patients who still meet the screening phase exclusion criteria 2) Residual toxicities of grade > 2 from previous treatments, with the exception of alopecia. 3) Major surgery within 30 days prior to entry into the study (excluding placement of vascular access or minor surgery within 14 days of entry into the study.
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1. Pazienti con metastasi cerebrali mote o sospette, a meno che non siano asintomatiche, siano state trattate con chirurgia e/o radioterapia, e siano stabili da almeno 2 settimana dall’inizio della terapia, senza l’utilizzo di corticosteroidi o anti convulsivi recidiva locale che può essere trattata con sola terapia chirurgica e/o radioterapia. 2. Storia di problematiche cardiache 3. Ipertensione non controllata 4. Partecipazione ad un altro trial clinico durante gli ultimi 30 giorni 5. Metastasi ossee come unico sito di malattia biopsiabile 6. Trattamento precedente con il trattamento in studio o farmaci di questa classe (es. Everolimus)
PAZIENTI RANDOMIZZATI NELLA FASE TERAPEUTICA 1) Pazienti che ancora incontrano I criteri di esclusione dello studio 2) tossicità residua di grado > 2 dal precedente trattamento, con eccezione di alopecia 3) chirurgia entro 30 giorni prima dell’arruolamento in studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free-survival |
sopravvivenza libera da progressione |
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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) |
Overall survival |
sopravvivenza globale |
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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 | 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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Il braccio standard sarà trattato con chemio/endocrino terapia a scelta dello sperimentatore tra i |
the standard arm is chemotherapy/endocrine treatment . the choise of treatment will be driven by the |
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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
| 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 | 1 |
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 | Information not present in EudraCT |
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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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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |