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) |
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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) |
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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 | 19.0 |
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 of the treatment of nivolumab in combination with ipilumumab 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. |
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E.2.2 | Secondary objectives of the trial |
To assess progression-free survival (PFS) all randomized subjects, overall and in, as determined by BICR, of nivolumab in combination with ipilimumab vs. nivolumab in combination with ipilimumab placebo for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall.
To assess overall survival (OS) of nivolumab combined with ipilimumab vs. nivolumab in combination with ipilimiumab placebo with for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall.
To assess efficacy (ORR, PFS and OS) by PD-L1 expression and HPV p-16 status of nivolumab in combination with ipilumumab compared to nivolumab in combination with ipilimumab placebo for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Confirmed squamous cell head and neck cancer
Widespread (metastatic) disease, or returned after previous treatment (recurrent)
No previous treatment for metastatic or recurrent disease
Tumor sample must be available for analysis of PDL1 and HPV (oropharynx only)
Performance status (ECOG 0-1) |
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) in the platinum refractory subgroup , by Blinded Independent Central Review (BICR)
Subjects that are platinum refractory are defined as:
-squamous cell cancer of the head and neck
-recurrence < 6 months after completion of previous platinum based chemotherapy
-no prior therapy for recurrent or metastatic disease
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall response rate (ORR) in the platinum eligible subgroup, by Blinded Independent Central Review (BICR)
Subjects that are platinum eligible are defined as:
-squamous cell cancer of the head and neck
-recurrence ≥6 months after completion of previous platinum based chemotherapy
-no prior therapy for recurrent or metastatic disease
Progression Free Survival (PFS) and Overall Survival (OS) in platinum eligible and refractory subgroups
Efficacy (ORR, OS, PFS), by PDL1 and HPV status, in platinum refractory and platinum eligible subgroups |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 25 |
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 |
Belgium |
Brazil |
Canada |
Czech Republic |
Finland |
France |
Ireland |
Netherlands |
Norway |
Romania |
Russian Federation |
South Africa |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |