E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced squamous cell carcinoma of the head and neck (SCCHN) |
|
E.1.1.1 | Medical condition in easily understood language |
Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells and develops in the mucous membranes (lining) of the different structures in the mouth, throat, and larynx |
|
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of atezolizumab compared with placebo based on independent review facility (IRF)-assessed event free survival (EFS) and overall survival (OS) |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of atezolizumab compared with placebo based on Investigator-assessed EFS, IRF and investigator-assessed EFS at 1 and 2 years and OS at 1, 2, and 3 years •To evaluate clinical benefit in atezolizumab compared with placebo in terms of impact on health-related quality of life and physical functioning •To evaluate the safety and tolerability of atezolizumab •To characterize the pharmacokinetics of atezolizumab •To evaluate the incidence and titers of anti-drug antibody(ADA) against atezolizumab
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age >= 18 years - Ability to comply with the study protocol, in the investigator's judgment - Histologically or cytologically confirmed squamous cell carcinoma of the head and neck SCCHN - Human papillomavirus (HPV) status - Completed definitive local therapy - Absence of metastatic disease as documented by radiographic scans - Adequate hematologic and end-organ function - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of study treatment. Women must refrain from donating eggs during this same period - Confirmed response of CR, PR, or SD to definitive local therapy documented in radiographic scans ≥ 8 weeks after completion of definitive local therapy
|
|
E.4 | Principal exclusion criteria |
- Patients who have received surgery alone or radiotherapy alone as definitive local therapy - Patients with oropharyngeal or oral cavity cancer who have persistent disease at the primary site post-concurrent CRT or post-RT - Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology - Evidence of disease progression or metastatic disease during or following definitive local therapy documented in the post-definitive local therapy screening scans - Uncontrolled or symptomatic hypercalcemia - Active or history of autoimmune disease or immune deficiency - Active tuberculosis - Significant cardiovascular disease - History of malignancy, including prior SCCHN primary tumors (other than current SCCHN) within 5 years prior to screening, Patients who have malignancies of a negligible risk of metastasis or death are eligible - Prior allogeneic stem cell or solid organ transplantation - Current treatment with anti-viral therapy for HBV - Prior neoadjuvant (i.e., induction) treatment or any systemic anticancer therapy without definitive local therapy for locally advanced head and neck cancer - Treatment with systemic immunostimulatory agents - Treatment with systemic immunosuppressive medication - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment - Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA approved agent as part of definitive local therapy unless the unapproved agent was given in addition to an approved agent as part of an induction regimen or as part of concurrent therapy with radiotherapy - Any systemic therapy after permitted definitive local therapies
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. IRF-assessed EFS 2. OS after randomization
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Approximately up to 84 months |
|
E.5.2 | Secondary end point(s) |
1. Investigator-assessed EFS 2. Change from baseline in physical function and Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer (EEORTC) Quality of Life Questionnaire over time while receiving treatment 3. Percentage of patients with adverse events 4. Serum concentration of atezolizumab at specified timepoints 5. Incidence of ADA response to atezolizumab
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Approximately up to 84 months 2. Baseline up until 30 days from last dose 3. Baseline until up to 90 days after end of treatment (approximately 1 year) 4-5. At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year) |
|
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Australia |
Brazil |
Canada |
China |
France |
Germany |
India |
Italy |
Korea, Republic of |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
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
|
The end of this study is defined as the date when all patients meet one of the following criteria: experienced an OS event, become lost to follow-up, withdrawn consent, or completed at least 60 months of follow-up after randomization, whichever occurs first. In addition, the Sponsor may decide to terminate the study at any time. |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |