| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Platinum-resistant ovarian cancer |
| Carcinoma ovarico platino-resistente |
|
| E.1.1.1 | Medical condition in easily understood language |
| Platinum-resistant ovarian cancer |
| Carcinoma ovarico platino-resistente |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10006888 |
| E.1.2 | Term | Ca ovary |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
| The primary objective is to compare the treatment groups in terms of progression free survival (PFS). |
| L’obiettivo primario è quello di comparare i gruppi di trattamento in termini di sopravvivenza libera da malattia (PFS). |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare the treatment groups in terms of:
- Overall survival (OS)
- Radiological response rate (in patients with measurable disease)
- Duration of response
- CA-125 response rate per GCIG and change in CA-125
- Toxicity profile
- Quality of Life assessments using FACT-O and FACT-O ovarian |
Gli obiettivi secondari sono quelli di comparare i gruppi di trattamento in termini di:
- Sopravvivenza globale (OS)
- Tasso di risposta radiologica (RR) (in pazienti con malattia misurabile)
- Durata della risposta
- Risposta sierologica del marcatore CA-125 secondo i criteri GCIG
- Tossicità
- Qualità di vita mediante la compilazione di questionari FACT-O and FACT-O per ovarian cancer-specific subscale (OCS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria:
1. Cytologic / histologic diagnosis of stage IC-IV epithelial , fallopian tube and primary peritoneal cancer (carcinosarcomas are included)
2. Patient who received 1-2 prior lines of treatments
3. Patient relapsed within 6 months after platinum containing regimen
4. Disease measurable or evaluable by RECIST version 1.1 or Ca 125 GCIG criteria
5. No residual peripheral neurotoxicity > Grade 1 from previous chemotherapy treatment
6. PS 0-1
7. Age >18 years.
8. Life expectancy of at least 3 months
9. Written informed consent prior to performance of study specific procedures or assessments
10. Ability and willingness to comply with treatment and follow up assessments and procedures
11. Adequate organ functions:
- Hematopoietic: Leukocytes > 2,500/mm3; Absolute neutrophil count >1,500/mm3; Platelets count >100,000/mm3; Hemoglobin >9 g/dL
- Hepatic: AST and ALT <3 times upper limit of normal (ULN)*; Alkaline phosphatase <3 times ULN*; Bilirubin <1.5 times ULN
*: <5 times ULN if liver metastases are present
- Renal: Creatinine clearance >45 mL/min
12. No other invasive malignancy within the past 3 years except non-melanoma skin cancer and in situ cervical cancer
13. Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule. |
Criteri d’inclusione:
1. Diagnosi citologica/istologica di carcinoma epiteliale ovarico, delle tube di Falloppio o primitivo del peritoneo, stadio IC-IV ( i carcinosarcomi sono inclusi);
2. Non più di 2 precedenti linee di chemioterapia;
3. Recidiva verificatasi entro 6 mesi dall’ultima linea a base di platino;
4. Malattia misurabile o valutabile secondo criteri RECIST 1.1 o criteri GCIG per Ca125;
5. Nessuna neurotossicità periferica residua > Grado 1 relativa a precedenti trattamenti chemioterapici;
6. ECOG performance status 0 o 1;
7. Pazienti con età = 18 anni;
8. Aspettativa di vita di almeno 3 mesi;
9. Firma del consenso informato;
10. Capacità e disponibilità a rispettare le valutazioni e le procedure richieste durante trattamento e follow-up;
11. Adeguate funzionalità d’organo, definite come di seguito:
- Emopoietica: Leucociti > 2,500/mm3; Neutrofili in valore assoluto = 1,500/mm3; Piastrine = 100,000/mm3; Emoglobina = 9 g/dl;
- Epatica: AST e ALT = 3 x ULN(upper limit normal)* ;Fosfatasi Alcalina = 3 x ULN* ; Bilirubina = 1.5 x ULN* N.B.: * < 5 x ULN se presenza di metastasi epatiche;
- Renale: Creatinine Clearance > 45 ml/min;
12. Nessun altra malignità invasiva negli ultimi 3 anni, fatta eccezione per carcinoma in situ della cervice o carcinoma basocellulare;
13. Assenza di qualsiasi condizione psicologica, familiare, sociale o geografica , che possa ostacolare la compliance al protocollo. |
|
| E.4 | Principal exclusion criteria |
Exclusion criteria:
1. Pregnant (potentially fertile patients must use contraceptive measures to avoid pregnancy during and for at least 3 months after study participation and must have a negative serum
pregnancy test at baseline).
2. Patients should not be breast-feeding during treatment and for 2 months following the end of treatment.
3. Serious heart disease, including heart failure, atrio-ventricular block of any degree, serious arrhythmia or history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
4. Active infection requiring antibiotics.
5. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
6. History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
7. Patients who had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with < Grade 2 neuropathy or = Grade 2 alopecia are an exception to this criterion and may qualify for the study.
8. Patients with evidence of interstitial lung disease.
9. Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedures such as fine needle aspiration or core biopsy within 1 week prior to beginning therapy are also excluded.
10. Known hypersensitivity to the study drugs or to drugs with similar chemical structures.
11. Concurrent treatment with other experimental drugs.
12. Participation in another clinical trial with any investigational drug within 30 days prior to study screening. |
Criteri d’esclusione:
1. Gravidanza (Le pazienti potenzialmente fertili devono usare essere un metodo contraccettivo per evitare una gravidanza durante lo studio e almeno fino a 3 mesi dopo la partecipazione in studio e devo avere un test di gravidanza sierico negativo al baseline);
2. Le pazienti non possono allattare durante il periodo di trattamento in studio e per i 2 mesi successive alla fine del trattamento;
3. Presenza di malattie cardiache serie, incluso insufficienza cardiaca, blocco atrio-atricolare di ogni grado, grave aritmia o storia di una o più delle seguenti condizioni cardiovascolari nei 6 mesi precedenti: angioplastica o stent coronarico, infarto del miocardio, angina instabile, malattia vascolare periferica sintomatica, bypass coronarico, insufficienza cardiaca congestizia di grado II, III o IV come definita dalla New York Heart Association (NYHA);
4. Infezioni attive che richiedono antibiotici;
5. Storia di malattia cerebrovascolare, embolia polmonare o trombosi venosa profonda non trattata (DVT) negli ultimi 6 mesi;
6. Nota infezione attiva da HIV, epatite B o C;
7. Pazienti che hanno ricevuto precedenti trattamenti chemioterapici, terapia target con piccole molecole o terapia radiante nelle 4 settimane precedenti il giorno 1 dello studio o non recupero a tossicità grado = 1 al basaline, da eventi avversi dovuti a un agente somministrato in precedenza. Note: Soggetti con neuropatia < Grado 2 o alopecia = Grado 2 sono eccezioni a questo criterio e possono essere incluse nello studio;
8. Pazienti con evidenza di malattia polmonare interstiziale;
9. Qualsiasi procedura chirurgica maggiore, biopsia a cielo aperto o lesioni traumatiche significative nelle 3 settimane precedenti l'inizio della terapia o nota necessità di intervento chirurgico maggiore durante il corso dello studio; sono escluse anche procedure minori quali: agoaspirato o biopsia percutanea nella settimana precedente il trattamento;
10. Nota ipersensibilità a qualsiasi farmaco o eccipiente previsto dello studio o a farmaci con struttura chimica simile;
11. Trattamento concomitante con altri farmaci sperimentali;
12. Partecipazione ad altra sperimentazione clinica con farmaco sperimentale nei 30 giorni precedent lo screening. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival (PFS) |
| Sopravvivenza libera da progressione |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| PFS will be measured from the date of randomization to the date of radiological/clinical progression of desease or death (whichever occurs first). |
| La PFS sarà misurata dalla data di randomizzazione alla data di progressione rediologica/clinica della malattia o alla morte (a seconda di ciò che si verifica per prima). |
|
| E.5.2 | Secondary end point(s) |
| Overall Survival (OS); Response Rate ; Patient reported outcome (PRO) |
| Sopravvivenza Globale; Tasso di risposta; Qualità della vita delle pazienti |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The OS will be measured from the date of randomization to the date of death.; The Response Rate will be measured for the whole study duration.; Whole study duration |
| La sopravvivenza globale sarà misurata dalla data di randomizzazione alla data di morte.; Il tasso di risposta sarà misurato per l'intera durata dello studio; Intera durata dello studio |
|
| 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 | 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 | 15 |
| 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 | 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 | 36 |
| 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 | 36 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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