E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ADVANCED OVARIAN CANCER |
CARCINOMA OVARICO IN FASE AVANZATA |
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E.1.1.1 | Medical condition in easily understood language |
ADVANCED OVARIAN CANCER |
CARCINOMA OVARICO 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054913 |
E.1.2 | Term | Serous cystadenocarcinoma ovary |
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 |
Proportion of patient alive at 12 months |
Proporzione delle pazienti vive a 12 mesi |
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E.2.2 | Secondary objectives of the trial |
PFS OS ORR (according to RECIST criteria version 1.1) TPST TSST Toxicity profile (evaluated according to NCI-CTCAE version 4.0) Quality of Life (QoL) (evaluated by EORTC QLQ-C30/ QLQ-OV28 questionnaire, FACT Ovarian Symptom Index (FOSI), FACT-ES and Activity daily living (ADL) and instrumental ADL (IADL) scales) |
Sopravvivenza globale Tasso di sopravvivenza Sopravvivenza libera da progressione TPST TSST Profilo di tossicità (valutato in accordo al CTCAE v4.0) QoL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female of 18 years of age or older • Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer • Platinum resistant or refractory disease (patients who did not respond to last platinum-based therapy or with last relapse occurred < 6 months from the last dose of platinum) or patients not amenable of platinum treatment • >3 previous chemotherapy lines • ECOG performance status 0 -2 • Measurable and evaluable disease according to RECIST criteria confirmed by radiological imaging: at least one lesion of = 1.0 cm for non-lymph nodes or = 1.5 cm in short-axis diameter for lymph nodes at CT scan (Subjects with isolated rising CA-125 without radiologically visible disease are excluded) • Left Ventricular Ejection Fraction (LVEF) = institutional lower limit normal • Estimated life expectancy = 16 weeks • Adequate functions evidenced by: ¬ Hemoglobin 10.0 g/dl ¬ Absolute neutrophil count 1.5 x 109/L ¬ White blood cells >3x109/L ¬ Platelet >100 x109/L ¬ AST and ALT 2.5 x Upper limit of normal, unless liver metastasis ¬ Bilirubin = 1.5 times the upper limit of normal (ULN) Estimated glomerular filtration 60mL/min • Patient able to comply with the treatment • Evidence of not pregnancy status as documented by a negative beta-human chorionic gonadotropin (ß-hCG) test • Not breastfeeding women Patients with child-bearing potential using (or willing to use) effective contraception during treatment and 3 months ahead unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically Comprehension and signature of the informed consent |
• Donne con età superiore ai 18 anni • Istologia o citologia che documenta un carcinoma epiteliale invasivo ovarico, primitivo peritoneale o delle tube di falloppio. • Platino resistenza o platino refrattarie o pazienti che non possono essere sottoposte al platino. • >3 precedenti line di chemioterapie • ECOG performance status 0 -2 • Malattia misurabile per I criteri RECIST 1.1(donne con rialzo isolato del CA-125 senza evidenza radiologica di patologia sono state escluse) • Left Ventricular Ejection Fraction (LVEF) = al valore inferior limite. Funzione d’organo adeguata |
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E.4 | Principal exclusion criteria |
• Subjects with borderline ovarian cancer • Subject with low malignant potential tumors • Less than 3 lines of previous therapies • Platinum sensitive disease (last relapse occurred > 6 months from the last dose of platinum) • Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy • History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer • Breastfeeding women • Pregnant women • Prior therapy with letrozole • Severe osteoporosis documented by Bone Mineral Density(BMD) T-score = -2.5 with existing fragility fracture(s) • Patients with a known hypersensitivity to Paclitaxel , PLD, Topotecan, Gemcitabine or Letrozole or any case of severe toxicity related to them. • Prior resistance to Paclitaxel , PLD, Topotecan, Gemcitabine • Patients with active hepatic disease (HCV or HBV infections), hepatic severe impairment or cirrhosis • Bowel obstruction, sub-occlusive disease, prior gastrectomy, symptomatic brain metastases • Myocardial infarct within six months before enrolment , NYHA Class II or worse heart failure, unstable angina, serious cardiac arrhythmia or cardiac arrhythmia requiring treatment • Any serious concomitant illness requiring treatment • Pre-existing peripheral neuropathy > CTCAE Grade 2 • Concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin) or strong CYP2A6 inhibitors (e.g. methoxsalen) because they may increase exposure to letrozole • Concomitant use of inducers of CYP3A4 (e.g. phenytoin, rifampicin, carbamazepine, phenobarbital, and St. John’s Wort) which may reduce exposure to letrozole Concomitant use of medicinal products with a narrow therapeutic index that are substrates for CYP2C19 (e.g. phenytoin, clopidrogel) that may have their systemic serum concentrations altered by letrozole |
• Donne con tumore ovarico borderline. Donne con patologia a basso grado di malignitià sono escluse. • Meno di 3 linee precedent di chemioterapia • Malattia platino senibile • Meno di 4 settimane dall’ultima dose di chemioterapia. • Storia di altra patologia neoplastica ( eccetto basalioma o carcinoma della cervice in situ adeguatamente trattato) History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) a meno che non sia stata accertata la remissione da più di 3 anni Osteoporosi severa |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patient alive at 12 months |
Proporzione delle pazienti vive a 12 mesi |
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E.5.1.1 | 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) | 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 | No |
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 | 32 |
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 | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |