| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
1.- Conventional high-grade chondrosarcoma (CS) (grade 2 or 3) and dedifferentiated chondrosarcoma (DDCS)
2.- Extraskeletal myxoid chondrosarcoma (EMC)
3.- Vascular sarcomas (VS) (including angiosarcoma, hemangioendothelioma and intimal sarcomas)
4.- Solitary fibrous tumor (SFT) (excluding dedifferentiated SFT)
5.- Clear cell sarcoma (CCS)
6.- Alveolar soft-part sarcoma (ASPS) |
1. Condrosarcoma convenzionale di alto grado (CS) grado 2 o 3 – e Condrosarcoma dedifferenziato (DDCS)
2. Condroscaroma mixoide extrascheletrico (EMC)
3. Sarcomi vascolari (VS) inclusi angiosarcoma, emandoendotelioma e sarcoma intimale
4. Tumore fibroso solitario (SFT) (escluso il SFT dedifferenziato)
5. Sarcoma a cellule chiare (CCS)
6. Sarcoma dei tessuti molli alveolare (ASPS) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Soft tissue sarcoma or bone sarcoma |
| Sarcoma dei tessuti molli o dell'osso in fase avanzata |
|
| 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 | 10068595 |
| E.1.2 | Term | Sarcoma metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
Stage 1 PHASE 1
The recommended dose of the sunitinib and nivolumab combination for phase II part will be determined by assessing adverse events according to CTCAE 4.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol
Stage 1 PHASE 2
• Progression-free survival rate: Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months
Stage 2 (Cohorts 1-6) PHASE 2
• CS/DDCS, EMC, VS, SFT, and CCS cohorts: 6-month progression-free survival rate Efficacy measured by the PFSR at 6 months according to RECIST 1.
• ASPS cohort: 12-month progression-free survival rate (PFSR): Efficacy measured by the PFSR at 12 months according to RECIST 1.1. PFSR at 12 months |
Stage 1 FASE 1
Determinare la dose raccomandata di sunitinib e nivoluman in combinazione da usare nella fase II dello studio
Stage 1 FASE 2
Valutare l’efficacia della combinazione di sunitinib e nivolumab in termini di tasso di sopravvivenza libera da progressione (PFSR) a 6 mesi, in pazienti con sarcoma dei tessuti molli e dell’osso in fase avanzata
Stage 2 FASE 2 Coorti 1-6
Valutare l’efficacia della combinazione di sunitinib e nivolumab in termini di tasso di sopravvivenza libera da progressione (PFSR) a 6 mesi, in pazienti con Condrosarcoma/condrosarcoma dedifferenziato, condroscaroma mixoide extrascheletrico, sarcoma vascolari, tumore fibroso solitario, sarcoma a cellule chiare, e a 12 mesi in pazienti con sarcoma dei tessuti molli alveolare |
|
| E.2.2 | Secondary objectives of the trial |
Stage 1PHASE 1
• Safety profile of the experimental treatment using CTCAE 4.0.
•PFSR:
•OS
•ORR
•Contribution to translational studies
Stage 1PHASE 2
•OS
•ORR
•Efficacy according to Choi criteria.
•Safety profile of the experimental treatment, through assessment of adverse event type using CTCAE 4.0.
•Clinical outcomes of post protocol treatments assessed by observation of such treatments in fup stage.
• Contribution to translational studies will be performed by providing biological
Stage 2 (Cohorts 1-6):PHASE 2
• OS
•ORR
•Safety profile of the experimental treatment using CTCAE 5.0.
•Clinical outcomes of post protocol treatments assessed by observation in fup stage.
• Correlation between efficacy and potential predictive biomarkers assessed by finding relationships between clinical efficacy results and translational data
• Prognostic and response correlation witth some biomarkers after 1 month, at progression, and at response.
•6-monts PFSR |
Stage 1 Fase 1
• Valutare il profilo di sicurezza secondo CTC-AE 4.0
• Valutare l’efficacia in termini di tasso PFSR a 6 mesi
• Valutare l'OS
• Determinare l' ORR
• Contribuire allo studio traslazionale
Stage 1 Fase 2
• Valutare l'OS
• Determinare l' ORR
• Valutare la risposta Choi
• Valutare il profilo di sicurezza secondo CTC-AE 4.0
Stage 2Fase 2
• OS
•ORR
•Profilo di sicurezza secondo CTC-AE 5.0
•Valutare gli esiti a fine trattamento
•Valutare la correlazione tra l’efficacia e il potenziale predittivo dei biomarcatori
•Valutare la correlazione prognostica e di risposta per alcuni indicatori biologici
•Valutare l’efficacia di aumento di sunitinib a dose superiore ) in combinazione con nivolumab dopo progressione alle dose raccomandata di sunitinib misurata in termini di di tasso di s(PFSR) a 6 mesi dopo l’aumento, nella coorte di pazienti affetti da condroscaroma (convenzionale/dedifferenziato)
•Valutare gli esiti a fine trattamento
•Contribuire allo studio traslazionale |
|
| 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 |
Other types of substudies
Specify title, date and version of each substudy with relative objectives: Translational study on response biomarkers
|
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sotto studio biologico traslazionale per l'analisi e ricerca di markers di risposta al trattamento
|
|
| E.3 | Principal inclusion criteria |
Stage 1
1. Patients must provide written informed consent
2. 18-80 years.
3. Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangioendothelioma, solitary fibrous tumor epithelioid sarcomas and extraskeletal myxoid chondrosarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing’s sarcoma, chondrosarcoma and dedifferentiated chondrosarcoma) confirmed by central pathology review.
4. Metastatic/advanced disease in progression in the last 6 months.
5. Measurable disease according to RECIST 1.1
7. ECOG of 0-1.
8. Adequate hepatic, renal, cardiac, and hematologic function.
9. LVEF
11. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to enrollment and agree to use birth control measuresPatients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
Stage 2 (Cohorts 1-6)
1. Patients (or legal tutors) must provide written informed consent
2. 12-80 years.
3. Diagnosis of conventional high-grade (grades 2 or 3) and dedifferentiated chondrosarcoma, extraskeletal myxoid chondrosarcoma, vascular sarcomas (including angiosarcoma, hemangioendothelioma and intimal sarcomas), sarcoma, and clear cell sarcoma confirmed by central pathology review.
4. Mandatory paraffin embedded tumor blocks must be provided for all subjects without exception for biomarker analysis before treatment (first biopsy) and at end of month 3 or earlier (second biopsy).
5. Metastatic/locally advanced unresectable disease in progression in the last 6 months according to RECIST 1.1. Patients with recent diagnosis of metastatic disease can be eligible (if they are not candidates to anthracycline-based treatment).
6. Patients should have previously received at least anthracyclines. Patients in the cohorts of subtypes sensitive to antiangiogenic therapy (SFT, ASPS, CCS, EMC or conventional CS/DDCS) are eligible even if not previously treated.
7. Previous therapy with antiangiogenics is allowed.
8. Measurable disease according to RECIST 1.1 criteria.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
10. Adequate hepatic, renal, cardiac, and hematologic function.
12. Left ventricular ejection fraction = 50% by echocardiogram or MUGA scan.
13. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and agree to use birth control measures during study treatment and for 6 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method |
Stage 1
1. Firma del consenso informato
2. Età 18-80 anni
3. Diagnosi istologica di sarcoma dei tessuti molli (sarcoma pleomorfo indifferenziato, sarcoma sinoviale, sarcoma alveolare dei tessuti molli, sarcoma a cellule chiare, angiosarcoma, emangiotelioma, tumore fibroso solitario, sarcoma epitelioide e condrosarcoma mixoide extrascheletrico) o sarcoma dell’osso (osteosarcoma, sarcoma dell’osso ad alto grado, sarcoma di Ewing’s condrosarcoma o condrosarcoma dedifferenziato)
4. Malattia metastatica/avanzata che è andata incontro a progressione negli 6 mesi precedenti.
5. Malattia misurabile secondoRECIST 1.1
6. ECOG 0-1
7. Adeguata funzionalità epatica, renale e cardiaca.
8. Adeguata funzionalità midollare
9. LVEF = 50%
10. Paz. femmine, potenzialmente fertili con test di gravidanza negativo entro le 24h dall’arruolamento e debbono accondiscendere all’utilizzo di un sistema per il controllo delle nascite durante tutto il periodo di trattamento. I pazienti sia maschi che femmine potenzialmente fertili debbono accettare di utilizzare un metodo anticoncezionale ritenuto efficace.
Stage 2
1. Firma del consenso informatostate condotte in accordo a quanto richiesto dal protocollo
2. Età 12-80 anni
3. Diagnosi Condrosarcoma convenzionale di alto grado (grado 2 o 3) e Condrosarcoma dedifferenziato, Condroscaroma mixoide extrascheletrico, Sarcomi vascolari (VS) -inclusi angiosarcoma, emandoendotelioma e sarcoma intimale-, Tumore fibroso solitario (SFT) (escluso il SFT dedifferenziato), Sarcoma a cellule chiare (CCS) e Sarcoma dei tessuti molli alveolare (ASPS) confermato dalla revisione patologica centralizzata.
4. Presenza obbligatoria, per tutti i pazienti, senza eccezioni) di un blocchetto di tessuto tumorale in paraffina per l’analisi dei biomarcatori prima del trattamento (materiale di archivio o biopsia ex-novo se non disponibile quello di archivio) e alla fine del 3 mese di trattamento o prima (seconda biopsia obbligatoria in corso di studio)
5. Malattia metastatica/avanzata che è andata incontro a progressione negli 6 mesi precedenti secondo i criteri RECIST 1.1. Pazienti con una recente diagnosi di malattia metastatica possono essere eleggibili (se non candidati ad un trattamento basato su antracicline)
6. I pazienti debbono avere ricevuto un trattamento con antracicline. I pazienti nelle coorti suscettibili ai trattamenti anti-angiogenici (SFT, ASPS, CCS, EMC o CS/DDCS) sono eleggibili se non precedentemente trattati.
7. E’ permessa una precedente terapia con anti-angiogenici
8. Malattia misurabile secondo i criteri RECIST 1.1
9. ECOG 0-1
10. Adeguata funzionalità epatica, renale, cardiaca ed ematologica
11. Adeguata funzionalità midollare
12. LVEF = 50%
13. Le pazienti di sesso femminile, potenzialmente fertili debbono avere un test di gravidanza sulle urine o sul siero, negativo 7 giorni prima dell’arruolamento e debbono accondiscendere all’utilizzo di un sistema per il controllo delle nascite durante tutto il periodo di trattamento e nei 7 mesi successivi al suo completamento. I pazienti sia maschi che femmine potenzialmente fertili debbono accettare di utilizzare un metodo anticoncezionale ritenuto efficace. |
|
| E.4 | Principal exclusion criteria |
Stage 1
1. Four or more previous lines of chemotherapy for the advanced disease.
2. Previous anti-PD-1, anti-PD-L1, anti PD-L2 or anti CTLA-4 antibody.
3. Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy
4. Active, known or suspected autoimmune disease.
5. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
6. Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).
7. Positive test for HBV sAg or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
8. Other disease or illness within the past 6 months, including any of the following:
• Myocardial infarction
• Severe or unstable angina
• Coronary or peripheral artery bypass graft
• Symptomatic congestive heart failure
• Cerebrovascular accident or TIA
• Pulmonary embolism
9. Evidence of a bleeding diathesis.
10. Ongoing cardiac dysrhythmias > G2.
11. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy.
12. Psychiatric illness or social situation that would preclude study compliance.
13. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
14. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
15. Hemorrhage = G 3 in the past 4 weeks.
16. History of allergy to study drug components.
17. Previous anticoagulants due to thrombotic events.
18. History of another cancer with the exception of adequately treated basal cell carcinoma or cervical cancer in situ.
19. Presence of brain or central nervous system metastases
Stage 2 (Cohorts 1-6)
1. 4 or more previous lines of chemotherapy.
2. Previous antiPD-1, anti-PD-L1 anti PD-L2 or anti CTLA-4 antibody.
3. Prior immune-related adverse event (G3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy
4. Active, known or suspected autoimmune disease.
5. A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
6. Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia, known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= G 3).
7. Positive test for HBV sA) or (HCV antibody indicating acute or chronic infection.
8. Other disease or illness within the past 6mo, including any of the following:
• MIA
• Severe or unstable angina
• Coronary or peripheral artery bypass graft
• Symptomatic congestive heart failure
• Cerebrovascular accident orTIA
• Pulmonary embolism
9. Evidence of a bleeding diathesis.
10. Uncontrolled hypertension,
11. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
12. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG |
Stage 1
1. 4 o più linee di chemioterapia per malattia avanzata
2. Precedenti trattamenti con anti PD-1, anti PD-L1, anti PD-L2 anticorpi anti CTLA-4
3. Precedenti AE immuno-correlati (polmoniti, epatiti, coliti, endocrinopatie immuno-correlate di G3 o superiore)
4. Malattia autoimmune attiva o nota
5. Condizione che richieda il trattamento sistemico con corticosteroidio con altri farmaci immunosoppressivi nei 14 ggg precedenti a terapia.
6. Malattie intremittenti non controllate, incluse (ma non limitate a): scompenso cardiaco congestiszio (CHF) NYHA classe III/IV, angina pectoris instabile o angioplastica coronarica, o inserzione di stent nelle 24 settimane precedente lo studio, aritmia cardiaca instabile, malattie psichiatriche note che potrebbero compromettere l’aderenza allo studio, defibrillatori intra-cardiaci, presenza nota di metastasi cardiache o anomalie delle valvole cardiache (di Grado =3)
7. Test positivo per HBV sAg o anticorpi HCV che indica infezione acuta o cronica.
8. Ogni altra patologia nei 6 mesi precedenti quale:
• Infarto miocardico
• Angina instabile o severa
• By pass coronarico o periferico
• Scompenso cardiaco congestizio sintomatico
• Ictus o attacco ischemico transiente
• Embolia polmonare
9. Evidenza di diasesi sanguinanti
10. Disaritme cardiache di G> 2
11. Ipertensione non controllata
12. Malattie psichiatriche o situazioni sociali che potrebbero precludere la compliance allo studio
13. Anormalità tiroidee pre-esistenti definite
14. Intervallo QTc prolungato all’ECG basale (QTc > 450 msec er maschi o QTc > 470 per femmine)
15. Emorragie di G =3 nelle precedenti 4 settimane
16. Storia di allergia ai componenti dei farmaci in studio
17. Precedente terapia anticoagulante a seguito di eventi trombotici
18. Storia di precedenti neoplasie ad eccezione del carcinoma delle cellule basali adeguatamente trattato o carcinoma della cervicale in situ.
19. Presenza di metastasi cerebrali o a livello del sistema nervoso centrale
Stage 2
1. 4 o più linee di chemioterapia per la malattia avanzata
2. Precedenti trattamenti con anti PD-1, anti PD-L1, anti PD-L2 anticorpi anti CTLA-4
3. Precedenti AE immuno-correlati (polmoniti, epatiti, coliti, endocrinopatie immuno-correlate di Grado 3 o superiore) manifestatesi in precedenti immunoterapie
4. Malattia autoimmune attiva o nota
5. Condizione che richieda il trattamento sistemico con corticosteroidi o con altri farmaci immunosoppressivi nei 14gg precedenti la terapia.
6. Malattie intermittenti non controllate, incluse (ma non limitate a): scompenso cardiaco congestizio (CHF) NYHA classe III/IV, angina pectoris instabile o angioplastica coronarica, o inserzione di stent nelle 24 settimane precedente lo studio, aritmia cardiaca instabile, malattie psichiatriche note che potrebbero compromettere l’aderenza allo studio, defibrillatori intra-cardiaci, presenza nota di metastasi cardiache o anomalie delle valvole cardiache (di Grado =3)
7. Test del virus dell’epatite B positivo per HBV sAg o anticorpi HCV che indica infezione acuta o cronica.
8. Ogni altra patologia nei 6 mesi precedenti quale:
• Infarto miocardico
• Angina instabile o severa
• By pass coronarico o periferico
• Scompenso cardiaco congestizio sintomatico
• Ictus o attacco ischemico transiente
• Embolia polmonare
9. Evidenza di diatesi sanguinanti
10. Ipertensione non controllata
11. Anormalità tiroidee pre-esistenti
12. Intervallo QTc prolungato all’ECG basale
13. Emorragie di G =3 nelle precedenti 4 settimane
14. Storia di allergia ai componenti dei farmaci in studio
15. Precedente terapia anticoagulante a seguito di eventi trombotici
16. Storia di precedenti neoplasie ad eccezione del carcinoma delle cellule basali adeguatamente trattato o carcinoma della cervicale in situ.
17. Presenza di metastasi cerebrali o nel sistema nervoso centrale
18. Mancata donazione del materiale bioptico al basale e dopo 3 mes |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Stage 1 PHASE 1
•The recommended dose of the sunitinib and nivolumab combination for phase II part will be determined by assessing adverse events according to CTCAE 4.0 t each cycle
Stage 1 P PHASE 2
•PFSR measured at 6 months after enrollment.
Stage 2 (Cohorts 1-6): PHASE 2
• CS/DDCS, EMC, VS, SFT, and CCS cohorts: PFSR measured at 6 months after enrollment
• ASPS cohort: PFSR measured at 12 months after enrollment |
Stage 1 FASE 1
• La dose raccomandata di sunitinib e nivolumab da utilizzare nella fase II sarà valuata, ad ogni ciclo, sulla base degli AEs (secondo CTCAE 4.0)
Stage 1 FASE 2
• PFSR sarà misurato a 6 mesi a partire dall'arruolamento
Stage 2 (Coorti 1-6): PHASE 2
• Nelle coorti CS/DDCS, EMC, VS, SFT, e CCS cohorts il PDSR sarà misurato a 6 mesi a partire dall'arruolamento
• Nella corte del ASPS cohort: sarà misurato a 12 mesi a partire dall'arruolamento |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Stage 1 PHASE 1
The recommended dose of the sunitinib and nivolumab combination for phase II part will be determined by assessing adverse events according to CTCAE 4.0 t each cycle
Stage 1 P PHASE 2
PFSR measured at 6 months after enrollment.
Stage 2 (Cohorts 1-6): PHASE 2
• CS/DDCS, EMC, VS, SFT, and CCS cohorts: PFSR measured at 6 months after enrollment
• ASPS cohort: PFSR measured at 12 months after enrollment |
Stage 1 FASE 1
La dose raccomandata di sunitinib e nivolumab da utilizzare nella fase II sarà valuata, ad ogni ciclo, sulla base degli AEs (secondo CTCAE 4.0)
Stage 1 FASE 2
PFSR sarà misurato a 6 mesi a partire dall'arruolamento
Stage 2 (Coorti 1-6): PHASE 2
• Nelle coorti CS/DDCS, EMC, VS, SFT, e CCS cohorts il PDSR sarà misurato a 6 mesi a partire dall'arruolamento
• Nella corte del ASPS cohort: sarà misurato a 12 mesi a partire dall'arruolamento |
|
| E.5.2 | Secondary end point(s) |
Stage 1 PHASE 1
• Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE 4.0.
• Progression-free survival rate (PFSR):
• Overall survival (OS)
• Overall Response Rate (ORR)
Stage 1 PHASE 2
• Overall survival (OS)
• Overall Response Rate (ORR):
• Efficacy according to Choi criteria.
• Safety profile according CTCAE 4.0.
• Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.
• Contribution to translational studies will be performed by providing biological samples.
Stage 2 (Cohorts 1-6): PHASE 2
• Overall survival (OS)
• Overall Response Rate (ORR):
• Safety profile of the experimental treatment using CTCAE 5.0.
• Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.
• Correlation between efficacy and potential predictive biomarkers assessed by finding relationships between clinical efficacy results and translational data
• Prognostic and response correlation with neutrophils/platelets; lymphocytes/platelets; and red blood cell distribution width (RDW), by assessing hematology tests at baseline, after 2 weeks (before nivolumab), after 1 month, at progression, and at response.
• 6-month progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since the date of enrollment until month 6 after enrollment |
Stage 1 FASE 1
• Profilo di sicurezza del trattamento secondo CTCAE 4.0.
• Progression-free survival rate (PFSR):
• Overall survival (OS): sopravvivenza valutata come decesso per ogni causa a partire dell'arruolamento
• Overall Response Rate (ORR): ) risposta in accordo ai RECIST 1.1
• Contributo alla ricerca traslazionale
Stage 1 FASE 2
• Overall survival (OS): sopravvivenza valutata come decesso per ogni causa a partire dell'arruolamento
• Overall Response Rate (ORR): risposta in accordo ai RECIST 1.1
• Efficacia secondo Choi
• Profilo di sicurezza: AEs secondo CTCAE 4.0.
• Outcomes clinici a fine trattamento valutati nella fase di fup
• Contributo alla traslazionale
Stage 2 (Coorti 1-6) Fase 2
• Overall survival (OS): sopravvivenza valutata come decesso per ogni causa a partire dell'arruolamento
• Overall Response Rate (ORR): ) risposta in accordo ai RECIST 1.1
• Profilo di sicurezza: AEs secondo CTCAE 5.0.
• Outcomes clinici a fine trattamento valutati nella fase di fup
• Correlazione con i biomarcatori valutati pre e post trattamento
• Corrlazione prognoscita e di risposta ad alcuni biomarcatori: pre e post trattamento
- PFSR at 6 Months |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stage 1 PHASE 1
- Safety profile: at each cycle
- PFSR at 6Mo
- OS : at tiime of death
- ORR every 3 months
- Efficacy according to Choi criteria.: every 3 months
- Contribution to translational studies at Mo3, at the response at EOT
Stage 1 PHASE 2
- OS : at tiime of death
- ORR every 3 months
- Efficacy measured through tumor response according to Choi criteria: Every 3 months
- Safety profile: at each cycle
- Clinical outcomes: During follow-up
- Contribution to translational studies at Mo3, at the response at EOT
Stage 2 (Cohorts 1-6): PHASE 2
OS : at tiime of death
- ORR every 3 months
- Safety profile: at each cycle
- Clinical outcomes: During follow-up
- Prognostic and response with biomarkers: t baseline, after 2wks, after 1Mo, at PD, and at response.
- PFSR at 6 Months |
Stage 1 PHASE 1
- Profilo di sicurezza: ad ogni ciclo
- PFSR a 6 Mesi
- OS : al momento del decesso
- ORR ogni 3 mesi
- Efficacia secondo Choi criteria: Eogni 3 mesi
- Contributo alla traslazionale: a mese 3, al tempo di risposta e al EOT
Stage 1 PHASE 2
- OS : al momento del decesso
- ORR ogni 3 mesi
- Efficacia secondo Choi criteria: Eogni 3 mesi
- Profilo di sicurezza: ad ogni ciclo
- Clinical outcomes: durante il fup
- Contributo alla traslazionale: a mese 3, al tempo di risposta e al EOT
Stage 2 (Coorti 1-6) FASE 2
- OS : al momento del decesso
- ORR ogni 3 mesi
- Profilo di sicurezza: ad ogni ciclo
- Clinical outcomes: durante il fup
- Predittività dei biomarcatori al baseline, after 2wks, a 1Mo, a PD, e alla risposta
- PFSR at 6 Months |
|
| 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 | 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) | 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 |
| Evaluation of the recommended dose for phase II |
| valutazione della Dose raccomandata di fase II |
|
| 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 | No |
| 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 | 7 |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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 |
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