E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced gynecological solid tumor |
Tumore ginecologico solido avanzato |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced gynecological solid tumor |
Tumore ginecologico solido avanzato |
|
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 | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
Best Overall Response Rate (Phase 2). |
Tasso di migliore risposta generale |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the acute and long-term safety and tolerability of the combination; • To further evaluate the preliminary efficacy of the combination in terms of duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) by RECIST v1.1 by investigator; • To characterize the PK profile of lucitanib when administered in combination with nivolumab. |
• Valutare la sicurezza e la tollerabilità in acuto e a lungo termine della combinazione; • Valutare in modo più approfondito l’efficacia preliminare della combinazione in termini di durata della risposta (duration of response, DOR), tasso di controllo della malattia (disease control rate, DCR), sopravvivenza libera da progressione (progression-free survival, PFS) e sopravvivenza globale (overall survival, OS) in base ai criteri RECIST v.1.1, secondo la valutazione dello sperimentatore; • Caratterizzare il profilo PK di lucitanib quando somministrato in combinazione con nivolumab; |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• = 18 years of age • Adequate organ function • Life expectancy = 3 months • Women of childbearing potential must have a negative serum pregnancy test • Advanced/metastatic solid tumor • Availability of tumor tissue at screening • ECOG performance status of 0 to 1 • Measurable disease (RECIST v1.1) • Advanced, recurrent, or metastatic gynecological solid tumor • Willing and able to provide an additional biopsy after 4 weeks of treatment |
- Avere un’età =18 anni al momento dell’ottenimento del consenso informato; - Avere un’adeguata funzionalità degli organi; - Avere un’aspettativa di vita di almeno 3 mesi - Per le donne in età fertile è richiesto un test di gravidanza sul siero negativo nei 3 giorni che precedono la somministrazione della prima dose del medicinale dello studio; - tumore solido avanzato/metastatico - disponibilità di tessuto tumorale allo screening - Performance status secondo ECOG da 0 a 2 - malattia misurabile (RECIST v1.1) - tumore ginecologico avanzato, ricorrente o metastatico - intenzionato e in grado di fornire una biopsia addizionale dopo 4 settimane di trattamento |
|
E.4 | Principal exclusion criteria |
• Prior treatment with lucitanib
• Active second malignancy
• Active central nervous system brain metastases
• Pre-existing duodenal stent or any gastrointestinal disorder
• Known history of HIV or AIDS; positive result of hepatitis B or C
viruses
• Evidence of interstitial lung disease, active pneumonitis,
myocarditis, or history of myocarditis
• Active, known, or suspected autoimmune disease (e.g.,
autoimmune hepatitis)
• Condition requiring systemic treatment with corticosteroids or
other immune suppressive medications
• Unstable or uncontrolled hypertension
(greater than 140/90 mmHg)
• Prior treatment with a VEGFR-tyrosine kinase inhibitor
|
Pazienti precedentemente trattati con lucitanib; tumore secondario attivo; metastasi attive al sistema nervosa centrale; stent duodenali pre-esistenti o qualunque disturbo gastrointestinale; storia nota di HIV o AIDS, risultato positivo per virus dell’epatite B o C; evidenza di malattia polmonare interstiziale, polmoniti attive, miocarditi o storia di miocarditi; patologie autoimmune attive, note o sospette; condizioni che richiedono trattamenti sistemici con corticosteroidi o altri trattamenti che sopprimono il Sistema immunitario; ipertensione instabile o incotrollabile (superiore a 140/90mmHg); trattamenti precedenti con inibitori del VEGFR tirosina chinasi. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed best overall response (PR or CR) based on investigator assessment or objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Conferma della migliore risposta (OR o CR) sulla base della valutazione dello sperimentatore o risposta obbiettiva in accordo del RECIST v1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From first dose of study drug until disease progression (up to approximately 2 years). |
Dalla prima dose fino a progressione della patologia ( fino circa 2 anni) |
|
E.5.2 | Secondary end point(s) |
1. Incidence of AEs, clinical lab abnormalities, and dose modifications. 2. Per RECIST v1.1: Duration of response, disease control, progression-free survival, overall survival. 3. Lucitanib PK parameters; AUC at steady state, Cmin, SS, Cmax, SS, and CL/F |
1. Incidenze degli eventi avversi, anomalie dei risutati clinici del laboratorio, e modificazioni della dose; 2. Secondo RECIST v1.1: durata della risposta, controllo della malattia, sopravvivenza libera da progressione, sopravvivenza complessiva; 3. area sotto la curva concentrazione plasmatica-tempo allo stato stazionario (AUCss), concentrazione minima allo stato stazionario (Cmin,ss), concentrazioni massime allo stato stazionario (Cmax,ss) e e clearance totale apparente del farmaco in seguito a somministrazione orale |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From first dose of study drug until disease progression (up to approximately 2 years). 2. From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years). 3. From first dose of study drug until the end of study (up to approximately 2 years). |
1. Dalla prima dose di farmaco in studio fino a progression della malattia ( fino a circa 2 anni); 2. Dalla prima dose di farmaco in studio fino almeno 100 giorni dopo la fine del trattamento (fino a circa 2 anni); 3. Dalla prima dose di farmaco in studio fino alla fine dello studio (fino a circa 2 anni). |
|
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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety, Efficacy, Pharmacokinetic, Therapy |
Sicurezza, Efficacia, Farmacocinetica, Terapia |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | Information not present in EudraCT |
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 |
United States |
Austria |
Belgium |
Germany |
Italy |
Spain |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |