E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal women with advanced breast cancer |
Donne in postmenopausa con carcinoma della mammella in stadio avanzato |
|
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 | 10057654 |
E.1.2 | Term | Breast cancer female |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
The primary objective is to assess the event-free survival (EFS) defined as the time from randomisation to progression, death without progression, loss to follow up, whichever occurred first. |
L'obiettivo principale dello studio e' di valutare la sicurezza e l'attivita' farmacologica della combinazione di vandetanib(100 o 300 mg/die o placebo) con fulvestrant (LD) nel prolungamento dell' sopravvivenza libera da eventi (Event-Free Survival EFS) in pazienti in postmenopausa con carcinoma della mammella in stadio avanzato. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are are to assess:
• Success rate at six months, defined as the percentage of patients without
progression and still on treatment at 24 weeks (progression, death without
progression, loss to follow up are all failures)
• Objective tumor Response rates (complete response, CR and partial response, PR)
according to RECIST criteria
• Time To Progression
• Progression Free Survival
• Overall survival
• Safety and tolerability of vandetanib / Placebo in combination with fulvestrant
• Quality of Life (EORTC QLQ-C30 questionnaire) |
·Il tasso di successi a 6 mesi.
·Il tasso di risposte tumorali obiettive (risposta completa [CR] e parziale [PR]) secondo i criteri RECIST.
·Il Tempo alla Progressione
·La sopravvivenza libera da progressione (Progression-Free Survival PFS)
·La sopravvivenza globale
·La tollerabilita' e la sicurezza. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent
2. Post menopausal woman, defined as a woman fulfilling any 1 of the following
criteria
3. Histologically or cytologically confirmed carcinoma of the breast
4. Patients with metastatic or locally advanced disease not amenable to therapy with
curative intent
5. Patients may have either measurable or non-measurable disease, as defined by
RECIST criteria
6. Must have estrogen receptor ER + and/or progesterone receptor PR+ on primary or
secondary tumour
7. Either patients relapsing during adjuvant treatment or patients presenting with
locally advanced or metastatic breast cancer
8. One previous chemotherapy for advanced disease is allowed (patients who have
stable but evident disease after chemotherapy are eligible)
9. One previous hormone therapy for advanced disease is allowed
10. Neoadjuvant or adjuvant therapy for breast cancer is allowed
11. Patients must have an ECOG PS < 2 and a life expectancy of at least 12 weeks. |
1.Rilascio del Consenso Informato Scritto
2.Donne in postmenopausa naturale o artificialmente indotta
3.Conferma istologica o citologica, di carcinoma della mammella
4.Pazienti con malattia metastatica o localmente avanzata
5.Patienti con malattia misurabile o non-misurabile, come definito dai criteri RECIST
6.Pazienti con Recettori per gli Estrogeni ER e/o per il Progesterone PgR positivi
7.Sia pazienti in ricaduta durante trattamento adiuvante sia pazienti con presenza di malattia metastatica o localmente advanzata
8.Una precedente chemioterapia per malattia avanzata e' ammessa (pazienti che sono stabili ma con malattia evidente dopo chemioterapia sono eleggibili)
9.Una precedente ormonoterapia per malattia avanzata e' ammessa
10.Sono ammesse precedenti terapie neoadiuvante o adiuvante
11.Performance Status ECOG 0-1-2 e aspettativa di vita di almeno 12 settimane. |
|
E.4 | Principal exclusion criteria |
1. Hormone receptor negative tumours (ER and PgR negative)
2. Prior therapy with fulvestrant or prior treatment with VEGFR TKIs (previous
treatment with bevacizumab [Avastin] is permitted)
3. More than one previous hormone-therapy for the advanced disease as defined
before
4. More than one previous chemo-therapy for the advanced disease as defined before
5. CNS metastases
6. Presence of life-threatening metastatic visceral disease, defined as extensive
hepaticinvolvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitic spread. Patients with discrete
pulmonary parenchymal metastases are eligible, provided their respiratory function
is not clinically and significantly compromised as a result of disease |
1.Pazienti con Recettori per gli Estrogeni ER e per il Progesterone PgR negativi
2.Precedente trattamento con Fulvestrant o con farmaci inibitori della tirosina chinasi del VEGFR (il precedente trattamento adiuvante con bevacizumab [Avastin] e' consentito)
3.Piu' di una precedente ormonoterapia per malattia avanzata
4.Piu' di una precedente chemioterapia per malattia avanzata
5.Metastasi cerebrali
6.Presenza di malattia metastatica viscerale life-threatening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is to assess the event-free survival (EFS) defined as the time from randomisation to progression, death without progression, loss to follow up, whichever occurred first. |
L'obiettivo primario di questo studio e' la sopravvivenza libera da eventi definita come tempo dalla randomizzazione alla progressione , morte in assenza di progressione o perdita di follow up. |
|
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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 18 |
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
| |
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 | 36 |
E.8.9.1 | In the Member State concerned days | 0 |