E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) |
Carcinoma a cellule squamose della testa e del collo ( SCCHN) metastatico o ricorrente |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) |
Carcinoma a cellule squamose della testa e del collo ( SCCHN) metastatico o ricorrente |
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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 | 10063569 |
E.1.2 | Term | Metastatic squamous cell carcinoma |
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 compare the ORR and assess the DoR of the treatment of nivolumab in combination with ipilimumab vs. nivolumab in combination with ipilimumab placebo, as determined by a blinded independent central review (BICR) using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria, for first line treatment of recurrent or metastatic SCCHN in the platinum refractory setting. |
Comparare l’ ORR e determinare la DoR del trattamento con nivolumab in combinazione con ipilimumab verso il nivolumab in combinazione con il placebo di ipilimumab, come determinato da una revisione centrale indipendente in cieco (BICR) utilizzando i criteri di valutazione alla risposta nei tumori solidi (RECIST 1.1), per il trattamento in prima linea del carcinoma a cellule squamose della testa e del collo metastatico o recidivante in un setting di pazienti refrattari al platino. |
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E.2.2 | Secondary objectives of the trial |
For 1st-line treatment of recurrent or metastatic SCCHN in the platinum eligible setting:to estimate the ORR and assess DOR of the treatment of nivo in combination with ipilimumab vs nivo in combination with ipilimumab placebo, as determined by BICR using RECIST1.1 criteria For 1st-line treatment of recurrent or metastatic SCCHN in the platinum eligible & platinum refractory settings, separately&overall,to assess: PFS all randomized subjects, overall&in, as determined by BICR, of nivo in combination with ipilimumab vs nivo in combination with ipilimumab placebo/OS of nivo +ipilimumab vs nivo +ipilimiumab placebo /efficacy (ORR,DOR,PFS,OS) by PD-L1 expression of nivo + ipilimumab compared to nivo + ipilimumab placebo /efficacy (ORR,DOR,PFS,OS) by HPVp-16 status of nivo + ipilimumab compared to nivo + ipilimumab placebo /To evaluate tumor mutation burden,as a potential predictive biomarker of efficacy of nivo in combination with ipilimumab or ipilimumab placebo |
For 1st-line treatment of recurrent or metastatic SCCHN in the platinum eligible setting:to estimate the ORR and assess DOR of the treatment of nivo in combination with ipilimumab vs nivo in combination with ipilimumab placebo, as determined by BICR using RECIST1.1 criteria For 1st-line treatment of recurrent or metastatic SCCHN in the platinum eligible & platinum refractory settings, separately&overall,to assess: PFS all randomized subjects, overall&in, as determined by BICR, of nivo in combination with ipilimumab vs nivo in combination with ipilimumab placebo/OS of nivo +ipilimumab vs nivo +ipilimiumab placebo /efficacy (ORR,DOR,PFS,OS) by PD-L1 expression of nivo + ipilimumab compared to nivo + ipilimumab placebo /efficacy (ORR,DOR,PFS,OS) by HPVp-16 status of nivo + ipilimumab compared to nivo + ipilimumab placebo /To evaluate tumor mutation burden,as a potential predictive biomarker of efficacy of nivo in combination with ipilimumab or ipilimumab placebo |
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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: REv Prot 04 Date: 25/05/2018 Title: A Double-Blind, Randomized, Two Arm Phase 2 Study of Nivolumab in Combination with Ipilimumab versus Nivolumab in Combination with Ipilimumab Placebo In Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Objectives: ooo
Pharmacogenomics Version: REv Prot 04 Date: 25/05/2018 Title: A Double-Blind, Randomized, Two Arm Phase 2 Study of Nivolumab in Combination with Ipilimumab versus Nivolumab in Combination with Ipilimumab Placebo In Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Objectives: ooo
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Farmacogenetica Versione: REv Prot 04 Data: 25/05/2018 Titolo: Studio di fase II in doppio cieco, randomizzato, a due bracci su nivolumab in combinazione con ipilimumab rispetto a nivolumab in combinazione con placebo di ipilimumab nel carcinoma a cellule squamose di testa e collo (SCCHN) ricorrente o metastatico. Sezione 5.8 Obiettivi: na
Farmacogenomica Versione: REv Prot 04 Data: 25/05/2018 Titolo: Studio di fase II in doppio cieco, randomizzato, a due bracci su nivolumab in combinazione con ipilimumab rispetto a nivolumab in combinazione con placebo di ipilimumab nel carcinoma a cellule squamose di testa e collo (SCCHN) ricorrente o metastatico. Sezione 5.8 Obiettivi: na
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E.3 | Principal inclusion criteria |
Confirmed squamous cell head and neck cancer Widespread (metastatic) disease, or returned after previous treatment (recurrent) Tumor sample must be available for analysis of PDL1 and HPV (oropharynx only) Performance status (ECOG 0-1) |
Conferma di carcinoma a cellule squamose della testa e del collo Malattia diffusa (metastatica) o ritornata dopo un precedente trattamento (recidivante)
Campione tumorale disponibile per l’ analisi del PD-L1 e HPV (solo orofaringe) Performance status (EGOG 0-1) |
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E.4 | Principal exclusion criteria |
Previous treatment of metastatic or recurrent disease Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin Any non-squamous subtype Active autoimmune disease Positive test for hepatitis B, C or HIV virus Previous treatment with checkpoint inhibitor drugs Active CNS metastases or carcinomatous meningitis |
Precedente trattamento per la malattia metastatica o recidivante Tumore derivante da uno dei seguenti siti primari: setto paranasale, nasofaringe, ghiandole salivari, cute Qualsiasi sottotipo non squamoso Malattia autoimmune attiva Test positivo per epatiti B, C o virus HIV Precedenti trattamenti con farmaci inibitori i checkpoints Metastasi attive nel SNC o meningite carcinomatosa |
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E.5 End points |
E.5.1 | Primary end point(s) |
1/ Overall response rate (ORR) in platinum refractory subgroup 2/ Duration of Response (DOR) in platinum refractory subgroup |
1/Tasso di risposta complessivo (ORR) nel sottogruppo refrattario al platino 2/ durata della risposta (DoR) nel sottogruppo refrattario al platino |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1/ and 2/ 28 months |
1/ e 2/ 28 mesi |
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E.5.2 | Secondary end point(s) |
1/ ORR in platinum eligible subgroup 2/ Progression Free Survival (PFS) in platinum eligible and refractory subgroups 3/ Overall Survival (OS) in platinum eligible and refractory subgroups 4/ DOR in platinum eligible subgroup 5/ Tumor mutation burden (TMB) in platinum eligible and refractory Subgroups |
1/Tasso di risposta complessivo (ORR) nel sottogruppo eleggibile al platino 2/ Progressione libera da malattia (PFS) nei sottogruppi eleggibili e refrattari al platino 3/ sopravvivenza globale (OS) nei sottogruppi eleggibili e refrattari al platino 4/ durata della risposta (DoR) nel sottogruppo eleggibile al platino 5/ Carico mutazionale del tumore (TMB) nei sottogruppo di pazienti eleggibili e refrattari al platino |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ 28 months 2/ 28 months 3/ 28 months 4/ 28 months 5/ 28 months |
1/ 28 mesi 2/ 28 mesi 3/ 28 mesi 4/ 28 mesi 5/ 28 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 | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Brazil |
Canada |
Russian Federation |
South Africa |
Turkey |
United States |
Belgium |
Finland |
France |
Ireland |
Netherlands |
Norway |
Romania |
Spain |
Sweden |
United Kingdom |
Czechia |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |