| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced epithelial ovarian cancer |
| carcinoma ovarico epiteliale in fase avanzata |
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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 | 10033128 |
| E.1.2 | Term | Ovarian cancer |
| 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 | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To show superiority of patupilone in overall survival compared to pegylated liposomal doxorubicin (Doxil/Caelyx) in taxane/platinum refractory/resistant patients with recurrent epithelial ovarian, primary fallopian or primary peritoneal cancer |
| Dimostrare la superiorita' del trattamento con patupilone sulla sopravvivenza globale, in confronto a doxorubicina liposomiale pegilato in pazienti con carcinoma epiteliale dell'ovaio primario tubarico o primario peritoneale, refrattario/resistente a taxano/platino |
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| E.2.2 | Secondary objectives of the trial |
| -To evaluate progression free survival (PFS) -To evaluate best overall response rate (CR, PR) according to modified RECIST criteria(Post-text supplement 1) -To evaluate CA-125 response for patients with evaluable disease as defined by Rustin criteria (Rustin 2003) -To evaluate duration of best overall response (CR, PR) -To evaluate time to progression (TTP) -To evaluate best overall response (CR, PR, SD, PD, Unknown) -To evaluate the safety and tolerability of patupilone administered in this dose and regimen and in this patient population -To evaluate detailed cardiac safety surveillance of a single dose of patupilone versus pegylated liposomal doxorubicin on QT interval (corrected and uncorrected), heart rate (HR) and cardiac conduction intervals (QRS, RR, and PR) in a limited number patients from selected study centers (Post-text supplement 2) -To conduct PK-PD analysis (see protocol) -To summarize the overall response by both RECIST and CA-125 as composite end-point |
| Valut la PFS-Valut la miglior risp glob(CR,PR)in base ai criteri RECIST modificati-Valut la risp CA-125 in paz con malatt valutabile def dai criteri di Rustin-Valut la durata della CR,PR-Valut il TTP-Valut la miglior risp glob(CR,PR,SD,PD,Sconosciuta)-Valut la sicur.e la toll di patupilone allo schema di dosagg utilizz-Valut la sicur.cardiaca di una dose singola di patupilone vs doxorubicina liposomiale pegilato sulla base dei parametri:intervallo QT(corretto e non corretto),freq cardiaca e intervalli di conduzione(QRS,RR e PR),in un num limitato di paz in centri selez(Post-text supplement 2)-Condurre an di PK/PD-Eseguire valut farmacogenomiche per esaminare se i livelli di espressione delle isoforme della beta-tubulina nelle cellule tumorali correla con la resistenza a patupilone-Valut i sintomi riferiti dalle paz e la QdV utilizzando il questionario FACT-O-Valut le Variaz dei sintomi della malattia mediante FOSI-Riassumere la risp glob mediante RECIST e CA-125 come endpoint compositi |
|
| 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 |
PHARMACOGENETIC:
Vers:finale
Date:2005/07/12
Title:
Objectives:
|
FARMACOGENETICA:
Vers:finale
Data:2005/07/12
Titolo:RICERCA SUI MARKER BIOLOGICI
Obiettivi:• To examine whether individual genetic variation in genes relating to drug metabolism, ovarian, primary fallopian, or primary peritoneal cancer, and the drug target pathway confer differential response to Patupilone. • To examine gene expression patterns, proteins, and metabolites of blood and tumor tissue that are associated with treatment response to Patupilone, or that possibly correlate with the severity or progression of ovarian, primary fallopian, or primary peritoneal cancer.
ALTRI SOTTOSTUDI:
STUDIO AGGIUNTIVO DI VALUTAZIONE DELLA SICUREZZA CARDIACA in un sotto-gruppo di 130 pazienti, da entrambi i gruppi di trattamento (patupilone (EPO906) e doxorubicina liposomiale)
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| E.3 | Principal inclusion criteria |
| 1.Histologically confirmed diagnosis of epithelial ovarian, primary fallopian or primary peritoneal cancer. 2. Resistant / refractory to prior taxane and intravenous or intraperitoneal platinum-based chemotherapy (up to three prior regimens) • Requirements for patients who have received one prior regimen: • Experienced disease progression during administration of, or within 6 months after administration of at least 4 cycles of one of the following first-line taxane/platinum based combination treatment regimens: • Initial dose of carboplatin at least AUC 5 - 6 administered IV, or cisplatin at least 75 mg/m2 administered IV, or cisplatin at least 75 mg/m2 administered IP. OR • Initial dose of cisplatin at least 75 mg/ m2 administered IP, and subsequently switched to an IV therapy with the first dose of at least 75 mg/ m2 (cisplatin) or at least AUC 5 (carboplatin). A third approved therapeutic agent (except anthracyclines) is permitted as part of the initial first line treatment, as a triplet regimen • Requirements for patients who have received two prior regimens: • First regimen as described above (see also section 3.3.1.1). • Second regimen must consist of a platinum salt as a single agent or in combination with either gemcitabine, paclitaxel, docetaxel, cyclophosphamide or topotecan. of at least 4 cycles of second line therapy, or may have experienced toxicity necessitating treatment discontinuation. • Requirements for patients who have received three prior regimens: • First regimen as described above (see also section 3.3.1.1). • Second regimen must consist of either platinum salt, gemcitabine, docetaxel, paclitaxel, cyclophosphamide or topotecan, administered as a single agent or in combination therapy. • Third regimen must consist of a platinum salt as a single agent or in combination with either gemcitabine, paclitaxel, cyclophosphamide or topotecan. Patients must have documented progression of disease during or within 6 months after the last dose of at least 4 cycles of third line therapy or may have experienced toxicity necessitating treatment discontinuation. • Patients treated with one taxane platinum-based regimen as a neo-adjuvant treatment and one other taxane-platinum-based regimen as an adjuvant therapy should be considered as having received only one regimen, providing that the adjuvant chemotherapy is initiated within 4 month after the completion of the neo-adjuvant therapy. • Patients who received consolidation and/or maintenance therapy with an approved agent are eligible provide that disease progression is documented within 6 months after the last dose of platinum-based chemotherapy. See protocolo for a complete list of inclusion criteria. |
| 1.Diagnosi confermata istologicamente di carcinoma epiteliale dell'ovaio, tubarico primario o peritoneale primario. 2. Resistenza/refrattarieta` alla precedente chemioterapia a base di platino endovenos a o intraperitoneale (fino a tre regimi precedenti). •Requisiti per le pazienti in trattamento precedente con un regime terapeutico: - progressione della malattia durante la somministrazione o entro 6 mesi dal completamento di almeno 4 cicli di uno dei seguenti regimi di trattamento di prima linea a base di taxano/cisplatino. - dose iniziale di carboplatino ev di almeno AUC 5-6 o cisplatino ev di almeno 75 mg/m2 o cisplatino intraperitoneale di almeno 75 mg/m2 OPPURE - dose iniziale di cisplatino intraperitoneale di almeno 75 mg/m2 e successivamente convertita a terapia ev con la prima dose di almeno 75 mg/m2 di cisplatino o almeno AUC 5 di carboplatino - un terzo farmaco approvato e` consentito come parte di un triplice regime terapeutico (eccetto antracicline) del trattamento di prima linea iniziale •Requisiti per le pazienti in trattamento precedente con due regimi terapeutici: o Primo regime terapeutico come descritto sopra (vedi anche Sezione 3.3.1.1). - Il secondo regime terapeutico deve comprendere sale di platino in monoterapia o in associazione a gemcitabina, paclitaxel, docetaxel, ciclofosfamide o topotecan. - Le pazienti devono presentare progressione della malattia documentata durante la somministrazione o nei 6 mesi successivi al trattamento chemioterapico di seconda linea (almeno 4 cicli) o devono aver manifestato tossicita` che ha richiesto la sospensione del trattamento. •Requisiti per le pazienti in trattamento precedente con tre regimi terapeutici: - Primo regime terapeutico come descritto sopra (vedi anche Sezione 3.3.1.1). - Il secondo regime terapeutico deve comprendere sale di platino in monoterapia o in associazione a gemcitabina, paclitaxel, ciclofosfamide o topotecan. - Il terzo regime deve comprendere sale di platino in monoterapia o in associazione a gemcitabina, paclitaxel, ciclofosfamide o topotecan. - Le pazienti devono presentare progressione della malattia documentata durante la somministrazione o nei 6 mesi successivi al trattamento chemioterapico di terza linea o devono aver manifestato tossicita` che ha richiesto la sospensione del trattamento. •Le pazienti trattate con un regime a base di taxano e platino come trattamento neo-adiuvante e un altro regime a base di taxano e platino come trattamento adiuvante devono essere considerate come se avessero ricevuto un solo regime, ammesso che la chemioterapia adiuvante sia stata iniziata entro 4 mesi dal completamento della terapia neo-adiuvante. •Le pazienti devono essere state trattate con terapia di consolidamento con un farmaco approvato e aver manifestato progressione della malattia documentata entro 6 mesi dalla somministrazione dell'ultima dose di chemioterapia a base di platino. Consultare il protocollo per la lista completa dei criteri di inclusione. |
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| E.4 | Principal exclusion criteria |
| 1. Patients with CA-125-only disease. 2. Unresolved bowel obstruction. 3. Not recovered fully from surgery for any cause. 4. Prior administration of epothilones, anthracyclines (including doxorubicin, epirubicin, daunorubicin, mitoxantrone), and/or pegylated liposomal doxorubicin. 5. Within 3 weeks of receiving any prior chemotherapy (including consolidation taxane therapy) or who are planning to receive other chemotherapy agents while participating in the study. 6. Within 3 weeks of receiving any prior radiotherapy or who are planning to receive radiotherapy while participating in the study. (Exception: Palliative radiotherapy of metastasis in extremities is allowed, but such lesions cannot be used as target lesions.) 7. Received any investigational compound within the past 28 days or who are planning to receive other investigational drugs while participating in the study. 8. Date of first study treatment would be more than 30 days past the screening CT scan (Screening CT scan must be performed within 6 months from last date of platinum-based chemotherapy) confirming disease progression. 9. Any peripheral neuropathy > CTC grade 1. 10. Unresolved diarrhea of any grade within last 7 days prior to start of treatment. 11. Presenting with symptomatic brain metastasis and/or leptomeningeal involvement. 12. Colostomy. 13. Underlying medical disease(s) that are not controlled [e.g. uncontrolled non-insulin dependant diabetes mellitus (NIDDM)]. 14. Known HIV positive status, and/or with the presence of an active or suspected acute or chronic uncontrolled infection. 15. Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease. 16. History of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ. 17. Receiving hematopoietic growth factors (except erythropoietin). 18. Concomitant administration of Coumadin or other agents containing warfarin, with the exception of low dose Coumadin (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports. (Wash-out period from therapeutic dose of Coumadin should be ≥ 7 days). See protocol for complete list of exclusion criteria. |
| 1.Pazienti solamente con malattia CA-125. 2. Occlusione intestinale in corso. 3.Guarigione incompleta da qualsiasi tipo di intervento chirurgico. 4. Somministrazione precedente: epotilone, antracicline (comprese doxorubicina, epirubicina, daunorubicina, mitoxantrone) e/o doxorubicina liposomiale pegilato. 5. Non possono essere arruolate pazienti prima di 3 settimane dalla somministrazione di qualsiasi chemioterapia precedente (compresa la terapia di consolidamento con taxano) o pazienti che devono ricevere altri farmaci chemioterapici durante lo studio. 6. Non possono essere arruolate pazienti sottoposte a radioterapia nelle 3 settimane precedenti o che devono essere sottoposte a radioterapia durante lo studio. (ad eccezione della radioterapia palliativa per le metastasi alle estremita`, tuttavia queste lesioni non possono essere utilizzate come lesioni di riferimento). 7. Pazienti che hanno ricevuto qualsiasi farmaco sperimentale negli ultimi 28 giorni o che devono ricevere trattamento sperimentale durante il periodo dello studio. 8. Primo trattamento in studio dopo un intervallo di tempo superiore a 30 giorni dalla data della conferma di progressione della malattia. 9. Neuropatia periferica > CTC Grado 1. 10. Diarrea di qualsiasi grado non risolta nei 7 giorni precedenti l'inizio della somministrazione del trattamento in studio. 11. Metastasi cerebrali sintomatiche e interessamento leptomeningeo. 12. Colostomia. 13. Condizioni cliniche di base non controllate (ad es.: diabete mellito non insulino-dipendente non controllato). 14. Positivita` nota all'HIV e/o presenza o sospetto di infezione non controllata acuta o cronica. 15. Scompenso cardiaco grave (NYHA III o IV), con cardiopatia o coronaropatia non controllate e/o instabili. 16. Anamnesi positiva per un'altra neoplasia maligna nei 5 anni precedenti l'ingresso nello studio ad eccezione delle lesioni cancerose cutanee non melanotiche trattate o carcinoma della cervice in situ. 17. Trattamento con fattori di crescita ematopoietici (ad eccezione dell'eritropoietina). 18. Somministrazione concomitante di Coumadin o altri composti contenenti warfarin, ad eccezione di basse dosi di Coumadin (1 mg o al giorno o inferiori). Il washout da dosi terapeutiche di Coumadin deve essere di >= 7 giorni. Consultare il protocollo per lista completa dei criteri di esclusione. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is overall survival. Overall survival time is measured from the day of randomization to the date of documented death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact. |
| Sopravvivenza globale. Il tempo di sopravvivenza viene misurato dal giorno della randomizzazione alla data di decesso indipendentemente dalla causa. In caso non si abbiano informazioni sul decesso la Sopravvivenza sara` troncata alla data dell'ultimo contatto. |
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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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 73 |
| 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 | 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
| |
| 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 | 51 |
| 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 | 51 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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