E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients aged 65 years or older with histologically or cytologically confirmed breast cancer, locally recurrent and/or metastatic; any estrogen/progesterone receptor status; HER2 receptor negative OR HER2 positive but with contraindication to anti-HER2 therapy |
prima linea di trattamento per il carcinoma della mammella avanzato nelle donne di età ≥65 anni |
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E.1.1.1 | Medical condition in easily understood language |
Patients aged 65 years or older with breast cancer, locally recurrent and/or metastatic |
prima linea di trattamento per il carcinoma della mammella avanzato nelle donne di età ≥65 anni |
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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 | 14.1 |
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 |
To evaluate the efficacy and impact on functional status of two different doses of nab-paclitaxel |
• Sopravvivenza libera da eventi (EFS). Un evento è definito come progressione di malattia o morte o comparsa di una limitazione funzionale (definita come perdita di almeno una funzione alle ADL/IADL rispetto al basale confermata al ciclo successivo e ritenuta legata al trattamento dall’investigatore) |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives
To evaluate the objective response rate (CR+PR) on the two nab-paclitaxel treatment arms
To evaluate the clinical benefit rate (CR+PR+SD) on the two nab-paclitaxel treatment arms
To evaluate the duration of progression-free survival and overall survival on the two nab-paclitaxel treatment arms
To evaluate the safety and tolerability for the two dosing regimens |
• valutare il tasso di risposta obiettiva (CR + PR) dei due regimi di nab-paclitaxel in pazienti con malattia misurabile
• valutare il tasso di beneficio clinico (CR + PR + SD) per i due regimi terapeutici in pazienti con malattia misurabile
• valutare la durata della sopravvivenza libera da progressione e sopravvivenza per i due regimi
• valutare la sicurezza e la tollerabilità dei due regimi alle diverse dosi. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically or cytologically confirmed breast cancer, locally recurrent and/or metastatic; any estrogen/progesterone receptor status; HER2 receptor negative OR HER2 positive but with contraindication to anti-HER2 therapy (e.g. known congestive cardiac failure).
• Measurable disease or non-measurable but evaluable disease according to RECIST 1.1 criteria (see Appendix B) [Eisenhauer]
• Age ≥ 65 years
• Female
• ECOG performance status 0-2
• Estimated life expectancy of ≥ 12 weeks
o Staging CT or MRI brain is required only if clinically indicated
• Adequate organ function
• No significant peripheral neuropathy (significant peripheral neuropathy is defined as ≥ grade 2 on CTCAE v4.0 criteria)
• No clinically significant comorbidities including: uncontrolled cardiac arrhythmias (with the exception of rate-controlled atrial fibrillation), NYHA class III or IV cardiac failure, uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
• No other malignancy within the last 5 years, with the exception of adequately treated non-melanomatous skin cancers, cervical intraepithelial neoplasia or cervical carcinoma in situ
• No requirements for concomitant medications or therapies that may potential interact with the trial agent. Any prohibited medication must be discontinued at least 14 days prior to trial entry
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. |
1) Diagnosi istologica o citologica di tumore della mammella localmente avanzato e / o metastatico, indipendentemente dallo stato recettoriale, HER2 negativo o HER2 positivo, con controindicazione alla terapia anti-HER2 (es. scompenso cardiaco congestizio).
2) malattia misurabile o valutabile secondo i criteri RECIST 1.1
3) Donna di età ≥ 65 anni
4) ECOG performance status 0-2
5) Aspettativa di vita stimata ≥ 12 settimane
6) Adeguata funzione d'organo,
7) Nessun pre-esistente neuropatia periferica significativa (significativa neuropatia periferica è definita come grado ≥ 2 su CTCAE v4.0 criteri)
8) Assenza di comorbidità clinicamente significative, tra cui: aritmie cardiache non controllate (tranne fibrillazione atriale cronica), classe NYHA III o IV insufficienza cardiaca, diabete non controllato, ipertensione o altre condizioni mediche che possono interferire con la valutazione della tossicità
9) Nessuna altra neoplasia negli ultimi 5 anni, con l'eccezione di tumori benigni della pelle, neoplasia cervicale intraepiteliale o carcinoma cervicale in situ
10) Nessun requisito per i farmaci o terapie concomitanti che possono potenzialmente interagire con l'agente di prova. Qualsiasi farmaco controindicato deve essere sospeso almeno 14 giorni prima dell'ingresso in studio
11) Assenza di qualsiasi condizione psicologica, familiare, sociologica o geografica che potenzialmente ostacolano il rispetto del protocollo di studio e il follow-up
12) Consenso informato scritto secondo le ICH / GCP e nazionali / locali in vigore prima della registrazione / randomizzazione. |
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E.4 | Principal exclusion criteria |
- active/symptomatic CNS metastases
- previous chemotherapy for breast cancer in the advanced setting |
- metastasi del sistema nervoso centrale sintomatiche
- precedente chemioterapia per malattia metastatica/avanzata |
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free survival (EFS) where an event is either disease progression or death or decline in functional status |
sopravvicenza libera da eventi |
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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) |
• Objective response rate (ORR)
• Clinical benefit rate (CBR)
• Progression free survival (PFS)
• Overall survival (OS)
• Incidence of Adverse events |
• valutare il tasso di risposta obiettiva
• valutare il tasso di beneficio clinico (CR + PR + SD)
• valutare la durata della sopravvivenza libera da progressione e sopravvivenza per i due regimi
• valutare la sicurezza e la tollerabilità dei due regimi |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
impact on function |
impatto sulla funzione |
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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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
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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
| 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 | 2 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 42 |
E.8.9.1 | In the Member State concerned days | 0 |