A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy after Definitive Local Therapy in Patients with High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

• Register: EUCTR
• Last refreshed on: 19 March 2018
• Main ID: EUCTR2017-003302-40-ES
• Date of registration: 13/03/2018
• Prospective Registration: Yes
• Primary sponsor: Roche Farma S.A.(Soc.Unipersonal)que realiza el ensayo en España y actúa como representante de F. Hoffmann-La Roche LTD
• Public title: A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy after Definitive Local Therapy in Patients with High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck
• Scientific title: A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB (ANTI?PD-L1 ANTIBODY) AS ADJUVANT THERAPY AFTER DEFINITIVE LOCAL THERAPY IN PATIENTS WITH HIGH-RISK LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
• Date of first enrolment: 14/03/2018
• Target sample size: 400
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003302-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Canada, China, France, Germany, India, Italy, Korea, Republic of, Poland, Russian Federation, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
-Age >= 18 years
-Ability to comply with the study protocol, in the investigator's judgment
-Histologically or cytologically confirmed SCCHN [Human papillomavirus (HPV) positive Stage III or HPV negative Stave IVA or IVB based on American Joint Committee on Cancer 8th Edition Cancer Staging Manual] involving the oral cavity, oropharynx, larynx, or hypopharynx
•HPV negative Stage IVA (T3/T4a ? N2M0) regardless of tobacco use history
•HPV negative Stage IVB (T3/T4a ? N3M0 or T4b ? N2/N3M0) regardless of tobacco use history
•HPV-positive oropharyngeal carcinoma Stage III (clinical T1/T2 ? N3M0) and >=10 years of tobacco use history
•HPV-positive oropharyngeal carcinoma Stage III (clinical T3/T4 ? N3M0 or pathologic T3/T4 ? N2M0) regardless of tobacco use history
- Human papillomavirus (HPV) status as determined locally by p16 immunohistochemistry, in situ hybridization, or by polymerase chain reaction-based assay
-Completed definitive local therapy and have scans 10-12 weeks after completion of definitive local therapy confirming either complete response, partial response, or stable disease and within 4 weeks of randomization
- Absence of metastatic disease as documented by radiographic scans
- Recovered from acute toxicities, except fatigue, xerostomia, dysgeusia, alopecia, associated with definitive treatment to Grade 1 or lower
- Patients with feeding tubes are eligible
- Availability of a representative pretreatment tumor specimen for exploratory biomarker research
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy >= 12 weeks
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative HIV test at screening
- Negative hepatitis B surface antigen test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion criteria:
- Patients who have received surgery alone as definitive local therapy
- HPV-negative patients who have a T1/T2 or N0/N1 tumor
- HPV-positive oropharyngeal carcinoma patients who have a clinical N0/N1/N2 or pathological N0/N1 nodal stage
- Patients, other than laryngeal cancer patients, who have persistent disease at the primary site and require salvage resection of primary tumor post chemoradiotherapy
- Squamous cell carcinoma of the nasopharynx
- Evidence of disease progression or metastatic disease during or following definitive local therapy documented in the 10- to 12-week post-definitive local therapy scans
- Uncontrolled or symptomatic hypercalcemia
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
- History of idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- Active tuberculosis
- Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ,or Stage I uterine cancer
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
- Current treatment with anti-viral therapy for HBV
- Prior neoadjuvant treatment or any systemic anti-cancer therapy without definitive local therapy for locally advanced head and neck cancer
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to initiation of study treatment
-Treatment with systemic immunosuppressive within 2 weeks prior to initiation of study treatment, or anticipation of need for systemi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally advanced squamous cell carcinoma of the head and neck (SCCHN)
MedDRA version: 20.0 Level: PT Classification code 10041823 Term: Squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Atezolizumab
Product Code: RO5541267/F03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A, Tecentriq
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: •To evaluate the efficacy of atezolizumab compared with placebo based on independent review facility (IRF)-assessed event free survival (EFS) and overall survival (OS)

Primary end point(s): 1. IRF-assessed EFS
2. OS after randomization

Secondary Objective: •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

Timepoint(s) of evaluation of this end point: 1-2. Approximately up to 84 months

Secondary Outcome(s)

Secondary end point(s): 1. Investigator-assessed EFS
2. IRF-assessed EFS and investigator-assessed EFS at 1 and 2 years
3. OS at 1, 2, and 3 years
4. Change from baseline in physical functioning over time while receiving treatment as assessed through use of the five-item Physical Functioning subscale (Questions 1?5) of the European Organisation for Research and Treatment of Cancer Quality-of-Life-Core- 30 Questionnaire (EORTC QLQ-C30)
5. Change from baseline in HRQoL over time while receiving treatment as assessed through use of the
two-item Global health status/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30
6. Incidence and severity of adverse events, including serious adverse events and immune-related adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0
7. Serum concentration of atezolizumab at specified timepoints
8. Incidence of ADA response to atezolizumab

Timepoint(s) of evaluation of this end point: 1. Approximately up to 84 months
2. At 1 and 2 years
3. At 1, 2, and 3 years
4-6. Approximately up to 84 months
7-8. Day 1 of Cycle 1, 2, 4, 8, 16 and at treatment discontinuation visit

Secondary ID(s)

WO40242

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.