E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer |
Tumore mammario |
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer |
Tumore mammario |
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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 | LLT |
E.1.2 | Classification code | 10065348 |
E.1.2 | Term | Breast adenocarcinoma 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 |
Activity evaluation of the full-oral metronomic schedule in terms of Clinical Benefit (CB=CR/PR/SD ≥24 weeks) |
Valutare l’attivita' della schedula metronomica full-oral in termini di Clinical Benefit (CB=CR/PR/SD ≥24 settimane) |
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E.2.2 | Secondary objectives of the trial |
PFS rate for 1 year Toxicity TTP Answer duration |
PFS rate a 1 anno Tossicita' TTP Durata della risposta |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
LIFE QUALITY:
Vers:
Date:
Title:Compliance to treatment
Objectives:Evaluate, using validated questionnaires, the compliance of the patients enrolled in the proposed experimental therapy
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QUALITA DELLA VITA:
Vers:
Data:
Titolo:Compliance al trattamento
Obiettivi:Valutare, tramite questionario validato, la compliance dei pazienti arruolati alla terapia sperimentale proposta
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E.3 | Principal inclusion criteria |
Presence of locally advanced or metastatic cancer not eligible for surgery or radiotherapy. Patients must have been previously treated with anthracyclines and taxanes for adiuvant or neoadiuvant and/or metastatic, or patients cannot be considered eligible to treatments with these drugs due to co-pathologies or clinical conditions. HER2 positive patients cannot be eligible to an anti Her2 treatment because of a severe reduction of ejection fraction or must not be eligible due to no other therapeutic options. AntiHER2 treatment has to be interrupted at least 4 weeks prior to enrolment. Patients can have been treated with hormontherapy in adiuvant and/or metastatic setting. Treatment has to be suspended at least 2 weeks bifore enrolment. Life expectancy > 24 weeks |
Presenza di malattia localmente avanzata o metastatica non candidabile ad intervento chirurgico o radioterapia. Le pazienti devono aver ricevuto precedenti trattamenti con antracicline e taxani per il setting adiuvante o neoadiuvante e/o metastatico oppure le pazienti devono essere considerate non candidabili al trattamento con tali farmaci in relazione a co-patologie o condizioni cliniche. Le pazienti HER2 positive non devono essere candidabili a trattamento anti Her2 per severa riduzione della frazione d’eiezione o non devono essere piu' candidabili per esaurimento delle opzioni terapeutiche. Il trattamento antiHER2 deve essere sospeso almeno 4 settimane prima dell’arruolamento. Le pazienti possono essere state trattate con ormonoterapia nel setting adiuvante e/o metastatico. Il trattamento deve essere interrotto almeno 2 settimane prima dell’arruolamento. Aspettativa di vita > 24 settimane. |
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E.4 | Principal exclusion criteria |
Absence of histology and biological characteristics of breast cancer. Presence of brain metastases and meningeal carcinomatosis. Radiotherapy required on bone lesions, in absence of other target lesions Previous treatment with capecitabine e/o vinorelbine. Serious historical hypersensitiveness to vinca alkaloids and/or to fluoropirimidines. Co-morbidity that contraindicates the use of fluorine pirimidine and/or vinca alkaloids. |
Assenza d’istologia o di caratterizzazione biologica della neoplasia mammaria Presenza di metastasi cerebrali e carcinosi meningea Necessita' di radioterapia su lesioni ossee, in assenza d’altre lesioni target Precedente trattamento con capecitabina e/o vinorelbina. Storia di severa ipersensibilita' agli alcaloidi della vinca e/o alle fluoropirimidine. Comorbidita' che controindichino l’utilizzo di fluoro pirimidine e/o alcaloidi della vinca. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the clinical benefit (CB ≥ 24 weeks) defined as the proportion of patients whose best response is comprehensive or complete response, partial response or stable disease maintained for a period greater than or equal to 24 weeks according to RECIST |
L’end point primario dello studio è il beneficio clinico (CB ≥24 settimane) definito come la proporzione di pazienti la cui miglior risposta globale sia o la risposta completa, risposta parziale o la stabilità di malattia mantenuta per un periodo superiore o uguale a 24 settimane in accordo ai criteri RECIST (VERS. 1.1). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
≥ 24 weeks |
≥ 24 settimane |
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E.5.2 | Secondary end point(s) |
1. The rate of progression-free survival at one year is defined as the proportion of patients from the date of enrollment to the next year had no tumor progression or death from any cause. For patients with measurable disease at baseline, the progression is determined by reference to the RECIST criteria (version 1.1). In the absence of measurable disease only for patients with metastatic bone progression will be defined as follows: a. Occurrence of one or more new bone lytic lesions b. Occurrence of one or more new lesions outside the bone c. Unequivocal progression of existing bone metastases. The occurrence of complications related to the presence of bone metastases will not be considered as evidence of disease progression if there are at least one of the three previous criteria. 2. Time to progression defined as the time between the date of enlistment and the date of documented progression of disease or death from any cause. 3. Duration of response, defined as the time between the date of first documented response (complete or partial response) and the date on which occurs the first progression or death from any cause. 4. The toxicity resulting from treatment will be determined by reference to the Common Terminology Criteria criteria (CTCAE) version 3.0. Will be reported on the incidence of adverse events, serious adverse events and changes from baseline in vital signs and laboratory values. 5. Quality of life. Will be given a specific questionnaire for assessing quality of life. 6. Adherence to treatment. There will be a diary that provides information about vinorelbine and capecitabine therapy, you take them and the problems related to them. |
1. Il tasso di sopravvivenza libera da progressione ad un anno definito come la proporzione di pazienti che dalla data d’arruolamento al successivo anno non hanno avuto progressione tumorale o morte per qualsiasi causa.
Per le pazienti con malattia misurabile al basale, la progressione è valutata in relazione ai criteri RECIST (versione 1.1).
In assenza di malattia misurabile per le pazienti con solo localizzazioni metastatiche ossee la progressione sarà definita come segue:
a. Comparsa di una o più nuove lesioni litiche ossee
b. Comparsa di una o più nuove lesioni al di fuori dell’osso
c. Progressione inequivocabile delle preesistenti metastasi ossee
La comparsa di complicanze legate alla presenza di metastasi ossee non sarà considerata come evidenza di progressione di malattia se non vi sono almeno uno dei tre criteri precedenti.
2. Tempo alla progressione definito come il tempo intercorrente tra la data di arruolamento e la data di progressione documentata di malattia o la morte per qualsiasi causa.
3. Durata della risposta, definita come il tempo intercorrente tra la data della prima documentata risposta (risposta parziale o completa) e la data in cui si verifica la prima progressione o la morte per qualsiasi causa.
4. La tossicità derivante dal trattamento che verrà valutata in relazione ai criteri Common Terminology Criteria (CTCAE) versione 3.0. Verranno riportati l’incidenza degli eventi avversi, gli eventi avversi seri e alterazioni rispetto al basale nei segni vitali e nei valori di laboratorio.
5. Qualità di vita. Sarà dato un questionario specifico per la valutazione della qualità di vita.
6. Aderenza al trattamento. Verrà dato un diario che fornisce informazioni riguardanti la terapia con vinorelbina e capecitabina, la loro assunzione e le problematiche a loro connesse. |
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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 | 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 | 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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
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 | 30 |
E.8.9.1 | In the Member State concerned days | 0 |