E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population will include participants with 1 of the following advanced or metastatic tumors approved for treatment with nivolumab monotherapy: non-small cell lung cancer (NSCLC); renal cell carcinoma (RCC); unresectable or metastatic melanoma; hepatocellular carcinoma (HCC); and microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC). |
La popolazione dello studio includerà partecipanti affetti da 1 dei seguenti tumori avanzati o metastatici approvati per il trattamento con nivolumab in monoterapia: carcinoma polmonare non a piccole cellule; carcinoma a cellule renali; melanoma non resecabile o metastatico; carcinoma epatocellulare; e carcinoma colorettale ad alta instabilità microsatellitare o con deficit nei meccanismi di riparo degli appaiamenti errati. |
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E.1.1.1 | Medical condition in easily understood language |
lung cancer; kidney cancer; melanoma; liver cancer; colorectal cancer |
cancro ai polmoni; cancro del rene; melanoma; cancro al fegato; cancro colonrettale |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal 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 describe the pharmacokinetics of nivolumab administered subcutaneously, with or without rHuPH20 |
Descrivere la farmacocinetica di nivolumab somministrato per via sottocutanea, con o senza rHuPH20 |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety profile of SC nivolumab
- To evaluate incidence of AEs in the broad scope MedDRA Anaphylactic Reaction SMQ and the select AE hypersensitivity/infusion reaction category
- To assess the immunogenicity of nivolumab |
Valutare il profilo di sicurezza di nivolumab SC Valutare l’incidenza di EA nell’ampio ambito di applicazione degli SMQ MedDRA per la reazione anafilattica, nonché nella categoria selezionata di EA del tipo ipersensibilità/reazione da infusione Valutare l’immunogenicità di nivolumab |
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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 |
Pharmacogenetics Version: RevProt01 Date: 05/07/2018 Title: n.a Objectives: This protocol will include residual sample storage for additional research (AR). For more details please refer to section 9.8.3 of the study protocol
Pharmacogenomics Version: RevProt01 Date: 05/07/2018 Title: n.a Objectives: This protocol will include residual sample storage for additional research (AR). For more details please refer to section 9.8.3 of the study protocol
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Farmacogenetica Versione: RevProt01 Data: 05/07/2018 Titolo: Studio farmacocinetico multitumorale di fase I/II della formulazione sottocutanea di nivolumab in monoterapia, sezione 9.8.3 Obiettivi: Questo protocollo includerà lo stoccaggio del campione residuo per ulteriori ricerche (AR). Per maggiori dettagli, fare riferimento alla sezione 9.8.3 del protocollo di studio.
Farmacogenomica Versione: RevProt01 Data: 05/07/2018 Titolo: Studio farmacocinetico multitumorale di fase I/II della formulazione sottocutanea di nivolumab in monoterapia, sezione 9.8.3 Obiettivi: Obiettivi: Questo protocollo includerà lo stoccaggio del campione residuo per ulteriori ricerche (AR). Per maggiori dettagli, fare riferimento alla sezione 9.8.3 del protocollo di studio.
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E.3 | Principal inclusion criteria |
- Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types:
1) Metastatic squamous or non-squamous NSCLC
2) Renal Cell Carcinoma, advanced or metastatic
3) Melanoma
4) Hepatocellular Carcinoma
5) Colorectal Cancer, metastatic (MSI-H or dMMR)
- Measurable disease as per RECIST version 1.1 criteria
- ECOG performance status of 0 or 1 |
- conferma istologica o citologica di uno dei seguenti tipi di tumore in stadio avanzato (metastatico e / o non resecabile): 1) NSCLC metastatico squamoso o non squamoso 2) Carcinoma a cellule renali, avanzato o metastatico 3) Melanoma 4) Carcinoma epatocellulare 5) Cancro colorettale, metastatico (MSI-H o dMMR) - Malattia misurabile secondo i criteri RECIST versione 1.1 - Stato di performance ECOG pari a 0 o 1 |
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E.4 | Principal exclusion criteria |
- Active brain metastases or leptomeningeal metastases
- Ocular melanoma
- Active, known, or suspected autoimmune disease
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- Metastasi cerebrali attive o metastasi leptomeningee - Melanoma oculare - Malattia autoimmune attiva, nota o sospetta |
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E.5 End points |
E.5.1 | Primary end point(s) |
Serum nivolumab:
-Cmax (Maximal concentration)
-Tmax (Time to maximal concentration)
-AUC(TAU) (Area under the concentration-time curve in one dosing interval)
-Ctau (observed serum nivolumab concentration at the end of the dosing interval) |
Nivolumab nel siero: -Cmax (concentrazione massima) -Tmax (tempo alla massima concentrazione) -AUC (TAU) (Area sotto la curva concentrazione-tempo nell’intervallo di un dosaggio) -Ctau (concentrazione osservata di nivolumab nel siero alla fine dell’ intervallo di dosaggio) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For all primary endpoints: approximately 1 year after Last Patient First Treatment |
Per tutti gli endpoint primari: circa 1 anno dopo il primo trattamento dell’ultimo paziente in studio |
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E.5.2 | Secondary end point(s) |
- Incidences of AEs, SAEs, AEs leading to discontinuation, deaths, and laboratory abnormalities
- Incidence of AEs in the MedDRA Anaphylactic Reaction broad scope SMQ occurring within 2 days after study drug administration
- Incidence of events within the hypersensitivity/infusion reaction select AE category occurring within 2 days after any study drug administration.
- Incidence of anti-nivolumab antibodies and neutralizing antibodies, if applicable |
-Incidenza di EA, SAE, EA che determinano interruzione, decessi e anomalie di laboratorio -Incidenza di EA nell’ampio ambito di applicazione degli SMQ MedDRA per reazione anafilattica verificatisi entro 2 giorni dopo la somministrazione del farmaco in studio -Incidenza di eventi nella categoria selezionata di EA del tipo ipersensibilità/reazione da infusione verificatisi entro 2 giorni dopo qualsiasi somministrazione del farmaco dello studio -Incidenza di anticorpi anti-nivolumab e anticorpi neutralizzanti, se pertinente |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all secondary endpoints: approximately 2 years after Last Patient First Treatment |
Per tutti gli endpoint secondari: circa 2 anni dopo il primo trattamento dell’ultimo paziente in studio |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Experience and Preference Questionnaire |
Esperienza del paziente e questionario sulle preferenze |
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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 |
pharmacokinetics (PK), safety, and tolerability of nivolumab SC with or without rhuPh20 |
farmacocinetica (PK), sicurezza e tollerabilità di nivolumab SC con o senza rhuPh20 |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
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 | 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 |
Chile |
New Zealand |
United States |
France |
Italy |
Poland |
Spain |
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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
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End of trial is defined as the last visit or scheduled procedure shown in the Schedule of Activities for the last participant (=last survival follow-up visit of the last participant) |
La fine dello studio è definita come l'ultima visita o procedura pianificata mostrata nella Schedula delle Attività del protocollo per l'ultimo partecipante (= ultimo controllo di sopravvivenza visita dell'ultimo partecipante) |
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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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |