E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Small Cell Lung Cancer |
Carcinoma polmonare a piccole cellule |
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E.1.1.1 | Medical condition in easily understood language |
Small cell lung cancer |
Carcinoma polmonare a piccole cellule |
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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 | LLT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung 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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate progression free survival (PFS) improvement for cabazitaxel compared to topotecan in patients with sensitive or resistant/refractory small cell lung cancer following a first line platinum based chemotherapy |
Dimostrare la sopravvivenza libera da progressione (PFS) di cabazitaxel rispetto a topotecan in pazienti con carcinoma polmonare a piccole cellule sensibili o resistenti/refrattari ad una prima linea di chemioterapia a base di platino. |
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E.2.2 | Secondary objectives of the trial |
o To assess disease progression free rate at 12 weeks o To assess Response Rate (RECIST 1.1) and duration of response o To assess Overall Survival (OS) o To assess the Safety (NCI-CTC version 4.03) o To assess the Health-Related Quality of Life (HRQoL) |
• Valutare la progressione libera dalla malattia a 12 settimane • Valutare la percentuale di risposta (RECIST 1.1) e durata della risposta • Valutare la sopravvivenza globale (OS) • Valutare la sicurezza (NCI-CTC versione 4.03) • Valutare la qualità della vita(HRQoL) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I 01. Histological/cytological proven locally advanced or metastatic small cell lung cancer with progressive disease during or after first line platinum based chemotherapy I 02. Male or female ≥18 years (or country's legal age of majority if >18 years) I 03. Patients with measurable disease, RECIST (version 1.1) I 04. ECOG performance status ≤1 |
I 01. Diagnosi dimostrata su base isto/citologica di carcinoma polmonare a piccole cellule localmente avanzato o metastatico in progressione durante o dopo una prima linea di chemioterapia a base di platino. I 02. Donne o uomini di età ≥18 anni I 03. Pazienti con aumento della malattia misurabile (RECIST 1.1.) I 04. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 |
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E.4 | Principal exclusion criteria |
E 01. Absence of signed and dated Institutional Review Board (IRB)-approved patient informed consent form prior to enrollment into the study. E 02. More than one prior chemotherapy regimen. Prior treatment with topotecan or taxanes. E 03. Less than 28 days elapsed from prior treatment with chemotherapy, radiotherapy or surgery to the time of randomization. (Radiotherapy for bone pain palliation is allowed). E 04. Adverse events (excluding alopecia) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.03) at the time of randomization. E 05. Uncontrolled CNS metastases: patients with CNS metastases may have previous irradiation, only patients with SD or objective response to irradiation who are without CNS symptoms and on a maximum steroid dose of dexamethasone 8 mg daily or equivalent can be included. E 06. Patients with known leptomeningeal metastases E 07. History of other, invasive neoplasm requiring ongoing therapy. E 08. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization E 09. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack. E 10. Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results E 11. Known HIV disease, or active hepatitis B or C (systematic testing is not required). E 12. Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization E 13. Patient with reproductive potential (M/F) who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 3 months after the completion of the study treatment. The definition of ''effective method of contraception'' will be based on the investigator's judgment. Effective method of contraception should also be adapted to local regulation. E 14. History of hypersensitivity to polysorbate 80 E 15. Inadequate organ and bone marrow function as evidenced by: o Hemoglobin <9.0 g/dL o Absolute neutrophil count <1.5 x 10 exp9/L o Platelet count <100 x 10exp9/L o AST/SGOT and/or ALT/SGPT >2.5 x ULN o AP >2.5 x ULN. In case of liver metastases AP > 5 x ULN o Total bilirubin >1.0 x ULN o Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula, and creatinine clearance <60 mL/min will exclude the patient |
E 01. Assenza di un C.I. del pz approvato dal C. E. firmato e datato prima dell’arruolamento nello studio. E 02. Più di un precedente regime chemioterapico. Un precedente trattamento con topotecan o taxani. E 03. Meno di 28 giorni trascorsi dal precedente trattamento con chemioterapia, radioterapia o intervento chirurgico alla data della randomizzazione (è consentita radioterapia palliativa del dolore osseo). E 04. Eventi avversi (ad eccezione dell’alopecia) dovuti a qualsiasi tipo di terapia antitumorale di grado > 1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] 4.03) al momento della randomizzazione. E 05. Metastasi cerebrali non controllate: i pazienti con metastasi al SNC possono aver ricevuto precedente trattamento radioterapico RX) solo in caso di malattia stabile o risposta obiettiva al RX in assenza di sintomi al SNC, ed essere in trattamento con una dose massima di steroidi pari o equivalente a desametasone 8 mg al giorno. E 06. I pz con note metastasi leptomeningee. E 07. Storia di altre neoplasie invasive che richiedano terapia. E 08. Partecipazione ad altri studi clinici e qualsiasi trattamento concomitante con altri farmaci sperimentali nei 30 gg precedenti la randomizzazione. E 09. nei 6 mesi precedenti la randomizzazione: infarto del miocardio, angina pectoris grave/instabile, bypass aortocoronarico o periferico, CHF di classe III o IV NYHA, ictus o attacco ischemico transitorio. E 10. Altre condizioni mediche gravi, acute o croniche, che possano limitare la capacità del paziente di partecipare allo studio o che possano interferire con l’interpretazione dei risultati dello studio E 11. Infezione nota da virus HIV, o epatiti B o C attive. Conferma laboratoristica non necessaria. E 12. Donne in gravidanza (definita da positività del test di gravidanza all’esame del sangue o all’esame delle urine) o in allattamento. E 13. Pazienti d’entrambi i sessi in età fertile che non accettino di utilizzare un metodo di contraccezione approvato ed efficace durante il periodo di trattamento sperimentale. La definizione di “metodo di contraccezione efficace” verrà lasciata al giudizio dello sperimentatore. Il metodo contraccettivo efficace individuato dovrà essere infine adattato alla normativa locale vigente. E 14. Anamnesi di ipersensibilità al polysorbato 80 E 15. Inadeguata funzionalità d’organo e midollare, diagnosticata in base a: • emoglobina <9.0 g/dL • conta assoluta dei neutrofili <1.5 x 109/L • conta piastrinica <100 x 10 exp9/L • AST/SGOT e/o ALT/SGPT >2.5 x ULN • Fosfatasi alcalina >2.5 x ULN. In caso di metastasi al fegato, fosfatasi alcalina>5 x ULN • Bilirubina totale > 1.0 x ULN • Creatinina sierica > 1,5 il limite superiore normale (ULN). In caso di creatinina pari a 1.0 – 1.5 x ULN, la clearance della creatinina sarà calcolata secondo la formula di Cockcroft-Gault. Un valore di clearance della creatinina < 60 mL/min è motivo di esclusione del paziente (vedi l’Appendice A) E 14. Anamnesi di ipersensibilità al polysorbato 80 E 15. Inadeguata funzionalità d’organo e midollare, diagnosticata in base a: • emoglobina <9.0 g/dL • conta assoluta dei neutrofili <1.5 x 109/L • conta piastrinica <100 x 109/L • AST/SGOT e/o ALT/SGPT >2.5 x ULN • Fosfatasi alcalina >2.5 x ULN. In caso di metastasi al fegato, fosfatasi alcalina>5 x ULN • Bilirubina totale > 1.0 x ULN • Creatinina sierica > 1,5 il limite superiore normale (ULN). In caso di creatinina pari a 1.0 – 1.5 x ULN, la clearance della creatinina sarà calcolata secondo la formula di Cockcroft-Gault. Un valore di clearance della creatinina < 60 mL/min è motivo di esclusione del paziente |
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival |
Sopravvivenza libera da progressione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 24 months |
fino a 24 mesi |
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E.5.2 | Secondary end point(s) |
Overall survival |
Sopravvivenza globale |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 24 months |
fino a 24 mesi |
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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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
Chile |
Korea, Republic of |
Russian Federation |
Ukraine |
United States |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 28 |
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 | 28 |
E.8.9.2 | In all countries concerned by the trial days | 0 |