E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
METASTATIC COLORECTAL CANCER |
CARCINOMA COLORETTALE METASTATICO |
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E.1.1.1 | Medical condition in easily understood language |
Advanced bowel cancer |
Tumore al colon avanzato |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 |
• Assessing early efficacy during the Maintenance Treatment Phase based on a 20% reduction in tumour size after 2 months of treatment
• Evaluating PFS
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All'interno di ciascuna coorte, lo studio ha i seguenti obiettivi co-primari di efficacia:
• Valutazione dell'efficacia iniziale durante la fase di trattamento di mantenimento in base a una riduzione del 20% della dimensione del tumore dopo 2 mesi di terapia
• Valutazione della sopravvivenza libera da progressione (PFS, progression-free survival)
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E.2.2 | Secondary objectives of the trial |
• OS
• ORR
• Disease control rate (DCR)
• Time to treatment response (TTR)
• Duration of response (DoR)
• ECOG performance status
• Incidence, nature and severity of adverse events (AEs) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients >/= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- At least 16 weeks of life expectancy at time of entry into the study
- Histologically confirmed metastatic colorectal cancer (CRC)
- Measureable, unresectable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
- No prior chemotherapy for CRC in the metastatic setting
- Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
- Adequate hematological, liver and renal function
- Agreement to use highly effective measures of contraception
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- ≥ 18 anni di età
- Stato ECOG ≤ 2
- Almeno 16 settimane di aspettativa di vita al momento dell'inclusione nello studio
- mCRC confermato istologicamente
- Malattia misurabile, non resecabile secondo i criteri RECIST 1.1
- Nessuna chemioterapia precedente per il CRC metastatico
- Blocco di tessuto tumorale primitivo fissato in formalina e incluso in paraffina (FFPET) conservato in archivio, prelevato al momento della diagnosi iniziale, disponibile per essere trasmesso al laboratorio designato
- Adeguata funzione epatica, renale, ematologica
- Utilizzo di metodi di contraccezione altamente efficaci
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E.4 | Principal exclusion criteria |
- Positive test for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C at Screening
- Active tuberculosis
- Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study
- Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is shorter, prior to start of maintenance treatment
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of maintenance treatment, or anticipated requirement for systemic immunosuppressive medications during the remainder of the study. The use of inhaled corticosteroids and mineralocorticoids is allowed.
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- Test positivo al virus dell'immunodeficienza umana (HIV).
- Forma attiva di Epatite B o Epatite C allo screening
- Tubercolosi attiva
- Somministrazione di un vaccino vivo attenuato nelle 4 settimane precedenti all'inizio del trattamento di mantenimento in studio o previsione della necessità di somministrazione di tale vaccino vivo attenuato durante lo studio
- Trattamento con agenti immunostimolatori sistemici (compresi, in via esemplificativa ma non limitativa, interferoni o interleuchina-2) nelle 4 settimane o nelle cinque emivite del farmaco, a seconda di quale sia il periodo più breve, precedenti all'inizio del trattamento di mantenimento in studio
- Trattamento con corticosteroidi sistemici o altri farmaci immunosoppressori sistemici nelle 2 settimane precedenti all'inizio del trattamento di mantenimento in studio o necessità di farmaci immunosoppressori sistemici durante lo studio. È ammesso l'uso inalatorio di corticosteroidi e di mineralcorticoidi
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Proportion of patients with a 20% reduction in tumor size in the Maintenance Treatment Phase after 2 months of treatment
2) Progression-free survival (PFS) |
1) Efficacia iniziale definita come percentuale di pazienti con una riduzione del 20% della dimensione del tumore
2) PFS
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) After two months of maintenance therapy
2) From randomization until disease progression ordeath from any cause |
1) dopo 2 mesi di trattamento nella fase di trattamento di mantenimento
2) dalla randomizzazione alla progressione della malattia valutata oppure al decesso per tutte le cause, a seconda di quale evento si verifichi per primo
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E.5.2 | Secondary end point(s) |
1) Overall survival
2) Overall response rate, calculated as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined according to RECIST 1.1
3) Disease control rate (DCR), calculated as the proportion of patients with a best overall response of CR, PR or stable disesase (SD) as determined according to RECIST 1.1
4) Time to treatment response (TTR), calculated as the time from randomization to the first occurrence of a documented objective response (CR or PR) determined according to RECIST 1.1
5) Duration of response (DoR), , defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first
6) Change in ECOG performance status
7) Incidence of adverse events (AEs) |
1) OS
2) ORR (risposta parziale o completa) La risposta sarà determinata dallo sperimentatore secondo i criteri RECIST 1.1.
3) DCR (risposta completa, risposta parziale o malattia stabile) determinata dallo sperimentatore secondo i criteri RECIST 1.1.
4) TTR, definito come il tempo trascorso dalla randomizzazione nella fase di trattamento di mantenimento alla prima documentazione successiva di risposta obiettiva (parziale o completa), determinata dallo sperimentatore secondo i criteri RECIST 1.1.
5) DOR, definita come il tempo trascorso dalla prima documentazione di una risposta obiettiva (parziale o completa) durante la fase di trattamento di mantenimento alla data della progressione, determinata dallo sperimentatore secondo i criteri RECIST 1.1, o al decesso per tutte le cause.
6) Performance status secondo l'ECOG durante e dopo il trattamento.
7) Incidenza di Eventi Avversi
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) From randomization until death from any cause
2) From randomization until disease progression
3) From randomization until disease progression
4) From randomization until disease progression or death from any cause
5) From randomization until disease progression or death from any cause
6) From baseline until end of study (up to 6 years)
7) From baseline until end of study (up to 6 years) |
1) dalla randomizzazione al decesso per tutte le cause
2) dalla randomizzazione alla progressione di malattia
3) dalla randomizzazione alla progressione di malattia
4) dalla randomizzazione alla progressione di malattia o al decesso per tutte le cause
5) dalla randomizzazione alla progressione di malattia o al decesso per tutte le cause
6) dalla baseline alla fine dello studio (fino a 6 anni)
7) dalla baseline alla fine dello studio (fino a 6 anni) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Assessment of dynamic biomarkers and genetic biomarkers |
Valutazione di di biomarkers dinamici e biomarkers genetici |
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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 | 4 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 144 |
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 |
Algeria |
Argentina |
Austria |
Belgium |
Brazil |
China |
Denmark |
Egypt |
France |
Germany |
Greece |
Italy |
Macedonia, the former Yugoslav Republic of |
Mexico |
Netherlands |
Poland |
Portugal |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Turkey |
United Kingdom |
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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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The end of the study is defined as the date when the last patient, last visit (LPLV) occurs at the end of the Post-treatment Follow-up. |
LPLV alla fine del follow-up post-trattamento |
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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 | 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 |