E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally recurrent or metastatic breast cancer |
Pazienti con carcinoma mammario recidivato localmente o metastatico |
|
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 | 10021977 |
E.1.2 | Term | Inflammatory carcinoma of breast recurrent |
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 of this study is to compare Overall Survival (OS) in patients treated with E7389 versus the Treatment of Physician's Choice (TPC, see Treatments' section for definition) in patients with locally recurrent or metastatic breast cancer. |
L'obiettivo principale di questo studio e' mettere a confronto la sopravvivenza globale (OS) nelle pazienti trattate con E7389 rispetto al trattamento di scelta del medico (TSM, vedere la sezione Trattamenti' per la definizione) in pazienti con carcinoma mammario recidivato localmente o metastatico. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess:
Progression Free Survival (PFS)
Objective Tumor Response Rate as measured using RECIST
criteria
Duration of Response
Safety Parameters (adverse events, laboratory parameters,
concomitant medication, and study drug exposure) |
Gli obiettivi secondari consistono nella valutazione:
della sopravvivenza libera da progressione (PFS)
del tasso di risposta tumorale obiettiva misurata in base ai Criteri RECIST
della durata della risposta
dei parametri di sicurezza (eventi avversi,parametri di laboratorio,trattamenti concomitanti ed esposizione al farmaco in studio). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Female patients with locally recurrent or metastatic breast cancer
who have received two to five prior chemotherapy regimens, which
must have contained an anthracycline and a taxane component, at
least 2 of which must have been given for locally recurrent or
metastatic disease. Patients must have proved refractory to the most
recent chemotherapy, documented by progression on or within six
(6) months of therapy
Patients with a known HER-2/neu over-expressing status may also
have been treated with trastuzumab. Patients with estrogen receptor
positive tumors may have been treated with anti-hormonals.
Previous chemotherapy, radiation, trastuzumab or hormonal therapy
must be discontinued three weeks before administration of E7389 or
TPC. |
Pazienti di sesso femminile con carcinoma mammario recidivato localmente o metastatico che siano state sottoposte ad almeno due ma a non piu' di cinque regimi chemioterapici, comprensivi di un'antraciclina e di un taxano, almeno 2 dei quali somministrati per la malattia recidivata localmente o metastatica. Deve essere stata dimostrata la refrattarieta' delle pazienti alle piu' recenti chemioterapie, documentata dalla progressione durante o entro sei (6) mesi dalla terapia
Le pazienti con una condizione accertata di iperespressione dell'HER-2/neu possono essere state trattate anche con trastuzumab. Le pazienti con positivita' del tumore per i recettori per gli estrogeni possono essere state trattate con farmaci antiormonali.
La chemioterapia, la radioterapia, il trastuzumab o l'ormonoterapia somministrati in precedenza devono essere sospesi tre settimane prima della somministrazione dell'E7389 o del TSM. |
|
E.4 | Principal exclusion criteria |
1. Patients who have received any of the following treatments within the specified period
before E7389 or TPC treatment start:
-chemotherapy, radiation, trastuzumab or hormonal therapy within three weeks
- any investigational drug within four weeks
2. Radiation therapy encompassing > 30% of marrow (Appendix 6)
3. Prior treatment with mitomycin C or nitrosourea
4. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring
active treatment, including the use of oxygen
5. Patients with brain or subdural metastases are not eligible, unless they have completed
local therapy and have discontinued the use of corticosteroids for this indication for at
least 4 weeks before starting treatment in this study. Any signs (e.g. radiologic) and/or
symptoms of brain metastases must be stable for at least 4 weeks.
6. Patients with meningeal carcinomatosis7. Patients who are receiving anti-coagulant therapy with warfarin or related compounds,
other than for line patency, and cannot be changed to heparin-based therapy, are not
eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT)
or international normalized ratio (INR) must be closely monitored.
8. Women who are pregnant or breast-feeding; women of childbearing potential with either
a positive pregnancy test at screening or no pregnancy test; women of childbearing
potential unless (1) surgically sterile or (2) using adequate measures of contraception in
the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least
12 months to be considered of non-childbearing potential.
9. Severe/uncontrolled intercurrent illness/infection
10. Significant cardiovascular impairment (history of congestive heart failure > NYHA
grade II, unstable angina or myocardial infarction within the past six months, or serious
cardiac arrhythmia) (Appendix 7)
11. Patients with organ allografts requiring immunosuppression
12. Patients with known positive HIV status
13. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or
non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively
treated ≥ 5 years previously with no subsequent evidence of recurrence
14. Patients with pre-existing neuropathy > Grade 2
15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical
derivative
16. Patients who participated in a prior E7389 clinical trial
17. Patients with other significant diseaseor disorders that, in the Investigator's opinion,
would exclude the patient from the study |
1. Pazienti che, prima del periodo specificato di somministrazione di E7389 o TPC, abbiano ricevuto uno dei seguenti trattamenti:
- chemioterapia, trattamento radiante, trastuzumeb od ormonoterapia tre settimane prima dell'arruolamento;
- farmaci sperimentali nelle quattro settimane precedenrti l'arruolamento.
2. Radioterapia midollare >30%.
3. Precedente terapia con mitomicina C o nitrosurea.
4. Linfangite polmonare che comporti non adeguata funzionalita' polmonare e richieda trattamento farmacologico, compresa la somministrazione di ossigeno.
5. Pazienti con metastasi cerebrali o subdurali, ad esclusione dei soggetti che abbiano completato la terapia locale o interrotto l'uso di corticosteroidi per questa indicazione per almeno 4 settimane prima dell'inizio dello studio. Qualsiasi evidenza (e.g. radiologica) e/o sintomi di metastasi cerebrali stabile per almeno 4 settimane.
6. Pazienti con carcinomatosi meningea.
7. Pazienti in terapia anticoagulante con warfarina o composti analoghi e che non possano passare a trattamento con eparina. Nel caso di soggetti che debbano proseguire warfarina a basso dosaggio e' necessario il monitoraggio stretto del tempo di protrombina (TP) e di INR.
8. Donne in gravidanza o allattamento; donne in eta' fertile con positivita' al test di gravidanza o in assenza di test; donne in eta' fertile non sterilizzate chirurgicamente o che non usino adeguati metodi contraccettivi a giudizio dell'Investigatore.
9. Grave/non controllata malattia/infezione ricorrente.
10. Significativa patologia cardiovascolare (storia di scompenso cardiaco congestizio > grado II NYHA, angina insatbile o infarto del miocardio nei 6 mesi precedenti l'arruolamento, o severa aritmia cardiaca) (Appendice 7).
11. Pazienti con trapioanto d'organo che necessitino di terapia immunosoppressiva.
12. Pazienti HIV positivi.
13. Pazienti con precedente diagnosi di neoplasia, diversa da carcinoma della cervice in situ, o carcinoma della pelle non-melanoma, esclusa una precedente neoplasia diagnosticata e trattata in via defin itiva >5 anni prima dell'arruolamento.
14. Pazienti con pregressa neuropatia > grado 2.
15. Pazienti con ipersensitivita' ad alicondrina B e/o a derivati di alicondrina B.
16. Pazienti che hanno precedentemente preso parte ad uno studio con E7389.
17. Pazienti con altre patologie significative che, a giudizio dell'Investigatore, ne rendano necessaria l'esclusione. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival is the primary endpoint. The study will be declared
positive, if at the final analysis, overall survival in the E7389 arm is
statistically significantly better compared to the TPC arm (p<0.05).
The p-value will be based on a two-sided, stratified log-rank test for
the ITT population. |
La sopravvivenza globale e' l'endpoint principale. Lo studio sara' dichiarato positivo se all'analisi conclusiva la sopravvivenza globale nel braccio dell'E7389 sara' migliore in modo statisticamente significativo rispetto al braccio del TSM (p<0,05). Il valore p sara' riferito a un test log-rank stratificato, a due code, per la popolazione ITT. |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 |
trattamento di scelta del medico |
|
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 | 6 |
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 | Information not present in EudraCT |
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 | 39 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 39 |
E.8.9.2 | In all countries concerned by the trial days | 0 |