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

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

This study will evaluate the efficacy and safety of atezolizumab compared with placebo as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (SCCHN)

Study Overview

• Status: Terminated
• Conditions: Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Intervention / Treatment: Drug: Atezolizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Victoria
    • North Melbourne, Victoria, Australia, 3051
      • Peter MacCallum Cancer Center
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Namur, Belgium, 5000
    • Clinique Ste-Elisabeth
• Brazil
  • BA
    • Salvador, BA, Brazil, 40050-410
      • Santa Casa de Misericordia de Salvador
  • PE
    • Recife, PE, Brazil, 50040-000
      • Hospital do Cancer de Pernambuco - HCP
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20560-120
      • Instituto Nacional de Cancer - INCa; Oncologia
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora Da Conceicao
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Health Sciences Centre
• China
  • Beijing, China, 100142
    • Beijing Cancer hospital
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Shanghai, China
    • Shanghai East Hospital
  • Shanghai, China, 200011
    • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wuhan City, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
• France
  • Avignon, France, 84082
    • Institut Sainte Catherine
  • Dijon, France, 21000
    • Centre Georges Francois Leclerc
  • Lyon, France, 69373
    • CENTRE LEON BERARD; Département d?Hématologie et d?Oncologie
  • Marseille, France, 13385
    • Hopital Timone Adultes; Oncologie Medicale Et Usp
  • Montpellier Cedex 5, France, 34298
    • ICM; Radiotherapie
  • Paris, France, 75970
    • Hopital Tenon; Oncologie Radiotherapie
  • Pessac, France, 33604
    • CHU Bordeaux
  • St Mande, France, 94160
    • Hôpitaux D'Instruction Des Armees Begin
  • VILLEJUIF Cedex, France, 94805
    • Gustave Roussy Cancer Campus; Radiotherapie
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde
  • München, Germany, 81377
    • Klinikum d. Uni. München; Campus Großhadern; Klinik und Poliklinik f. Strahlenthera. und Radioonko
  • Rostock, Germany, 18059
    • Universitätsmedizin Rostock, Klinik und Poliklinik für Strahlentherapie; Zentrum für Radiologie
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologial Intezet; Onkologiai Osztaly X
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Kórház
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
• India
  • Haryana
    • Gurgaon, Haryana, India, 122001
      • Medanta-The Medicity
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Hospital; Dept of Medical Oncology
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Fondazione G. Pascale; S.C. Oncol. Medica Testa-Collo e Sarcoma
  • Emilia-Romagna
    • Lugo, Emilia-Romagna, Italy, 48022
      • Ospedale Umberto I ASL di Ravenna Presidio Ospedaliero di Lugo
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
  • Liguria
    • Savona, Liguria, Italy, 17100
      • Ospedale Civile; Servizio Oncologia
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Spedali Civili di Brescia
    • Milano, Lombardia, Italy, 20142
      • Asst Santi Paolo E Carlo; Unita Operativa Di Oncologia Medica
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto IRCCS
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Hyogo, Japan, 650-0017
    • Kobe University Hospital
  • Miyagi, Japan, 981-1293
    • Miyagi Cancer Center
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of Jfcr
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
  • Gliwice, Poland, 44-101
    • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
  • Warszawa, Poland, 02-781
    • Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowotworów G?owy i Szyi
• Portugal
  • Coimbra, Portugal, 3000-075
    • IPO de Coimbra; Servico de Oncologia Medica
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Russian Federation
  • Novosibirsk, Russian Federation, 630108
    • Novosibirsk Regional Oncological Dispancer
  • Omsk, Russian Federation, 644013
    • Bhi of Omsk Region Clinical Oncology Dispensary
  • Tomsk, Russian Federation, 634028
    • Tomsk scientific research institute of oncology SO RAMN, PAD; Pathological
  • Krasnodar
    • Krasnoyarsk, Krasnodar, Russian Federation, 660133
      • Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moskovskaja Oblast, Russian Federation, 105229
      • Main Military Clinical Hospital named after N.N. Burdenko
    • Moscow, Moskovskaja Oblast, Russian Federation, 125248
      • P.A. Herzen Oncological Inst. ; Oncology
    • Moskva, Moskovskaja Oblast, Russian Federation, 125367
      • FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.
    • Moskva, Moskovskaja Oblast, Russian Federation, 119435
      • First MSMU n.a. Sechenov Univercity Hospital 1; Plastic surgery
  • Sankt Petersburg
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, 197758
      • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
  • Sverdlovsk
    • Ekaterinburg, Sverdlovsk, Russian Federation, 620905
      • Sverdlovsk Regional Oncology Dispensary; Chemotherapy
• South Africa
  • Cape Town, South Africa, 7530
    • Tygerberg Hospital; Oncology Dept
  • George, South Africa, 6530
    • GVI Oncology Outeniqua Unit
  • Mayville, South Africa, 4001
    • The Oncology Centre; Haematology - Radiation Oncology
  • Pretoria, South Africa, 0002
    • Steve Biko Academic Hospital; Oncology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
  • Sevilla, Spain, 41014
    • Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe; Servicio de Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital;Oncology and Hematology Office Critical Care Center, 14H
  • Taichung, Taiwan
    • Taichung Veterans General Hospital; Radiation Oncology
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital; Oncology
  • Taipei, Taiwan, 112
    • Division of Hematology and Oncology, Taipei Veterans General Hospital
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital; Oncology
• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi
  • Ankara, Turkey, 06200
    • Dr. Abdurrahman Yurtarslan Oncology Hospital; 2nd Oncology Clinic
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty, Oncology Hospital
  • Kar?iyaka, Turkey, 35575
    • ?zmir Medical Point; Oncology
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Oncology Center
  • Kiev, Ukraine, 03115
    • Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients
  • Kryvyi Rih, Ukraine, 50048
    • ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department
  • Lviv, Ukraine, 79031
    • Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy
  • Sumy, Ukraine, 40005
    • RCI Sumy Regional Clinical Oncological Dispensary
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61070
      • Municipal Noncommercial Institution Regional Center of Oncology
  • Podolia Governorate
    • Vinnytsya, Podolia Governorate, Ukraine, 21029
      • Vinnytsya Regional Clinical Oncology Dispensary
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary; Medical Oncology Dept
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Fulham
  • Plymouth, United Kingdom, PL6 8BT
    • Derriford Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • University of California San Diego Medical Center; Moores Cancer Center
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute of Baptist Health, Inc.
    • Pensacola, Florida, United States, 32503
      • Woodlands Medical Specialists, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Winship Cancer Institute of Emory University
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
  • Kansas
    • Wichita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic; Taussig Cancer Institute
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Histologically or cytologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Human Papilloma Virus (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 Complete Response (CR), Partial Response (PR), or Stable Disease (SD) to definitive local therapy documented by CT with contrast or MRI with contract to head and neck region done >= 8 weeks after completion of definitive local therapy and within 28 days prior to initiation of study drug.

Exclusion Criteria:

• Patients who have received surgery alone or radiotherapy alone as definitive local therapy
• 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 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 within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Prior allogeneic stem cell or solid organ transplantation
• Current treatment with anti-viral therapy for Hepatitis B Virus (HBV)
• 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
• Any systemic therapies after permitted definitive local therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atezolizumab; Participants will receive Atezolizumab for 16 cycles, or up to 1 year (whichever occurs first)	Drug: Atezolizumab; Atezolizumab intravenous infusion will be administered at a fixed dose on Day 1 of each 21-day cycle for 16 cycles.
Experimental: Placebo; Participants will receive Placebo for 16 cycles, or up to 1 year (whichever occurs first).	Drug: Placebo; Placebo intravenous infusion will be administered a fixed dose on Day 1 of each 21-day cycle for 16 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Investigator-assessed Event Free Survival (EFS)	Randomization to the first documented disease recurrence, or disease progression (per Response Evaluation Criteria In Solid Tumors (RECIST v1.1)), or death from any cause, whichever occurs first, through the end of study (approximately 65 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS) after Randomization	Randomization to death from any cause, through the end of study (approximately 99 months)
Independent Review Facility-assessed Event Free Survival (IRF-assessed EFS)	Randomization to the first documented disease recurrence, or disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, through the end of study (approximately 65 months)
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 (EORTC) Quality of Life Questionnaire	Baseline to 3 Months and 6 Months
Percentage of Participants with Adverse Events	Baseline until up to 90 days after end of treatment (approximately 99 months)
Serum Concentration of Atezolizumab	At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year).
Incidence of ADA Response to Atezolizumab	At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year).

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): March 6, 2024

Study Registration Dates

• First Submitted: February 25, 2018
• First Submitted That Met QC Criteria: February 28, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: WO40242; 2017-003302-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No