Clinical trial NCT03452137: 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
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-03-02
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: Investigator-Assessed Event-Free Survival (INV-assessed EFS)
timeFrame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause (up to 5 years, 5 months)
measure: Independent Review Facility (IRF) Assessed EFS
timeFrame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
measure: Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years
timeFrame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
measure: Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years
timeFrame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
measure: Percentage of Participants Event-Free for OS at 2, 3, and 5 Years
timeFrame: From randomization to OS event or date last known to be alive at 2, 3, and 5 Years
measure: Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score
timeFrame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
measure: Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score
timeFrame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)
measure: Serum Concentration of Atezolizumab
timeFrame: Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year)
measure: Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab
timeFrame: Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center; Moores Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Miami
country: United States
facility: Miami Cancer Institute of Baptist Health, Inc.
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, P.A.
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
state: Georgia
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Billings
country: United States
facility: Billings Clinic Research Center
state: Montana
city: Cleveland
country: United States
facility: Cleveland Clinic; Taussig Cancer Institute
state: Ohio
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Salvador
country: Brazil
facility: Santa Casa de Misericordia de Salvador
state: BA
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: PE
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa; Oncologia
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lyon
country: France
facility: CENTRE LEON BERARD; Département d?Hématologie et d?Oncologie
city: Marseille
country: France
facility: Hopital Timone Adultes; Oncologie Medicale Et Usp
city: Montpellier Cedex 5
country: France
facility: ICM; Radiotherapie
city: Paris
country: France
facility: Hopital Tenon; Oncologie Radiotherapie
city: Pessac
country: France
facility: CHU Bordeaux
city: St Mande
country: France
facility: Hôpitaux D'Instruction Des Armees Begin
city: VILLEJUIF Cedex
country: France
facility: Gustave Roussy Cancer Campus; Radiotherapie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde
city: München
country: Germany
facility: Klinikum d. Uni. München; Campus Großhadern; Klinik und Poliklinik f. Strahlenthera. und Radioonko
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Klinik und Poliklinik für Strahlentherapie; Zentrum für Radiologie
city: Budapest
country: Hungary
facility: Orszagos Onkologial Intezet; Onkologiai Osztaly X
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Kórház
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
city: Gurgaon
country: India
facility: Medanta-The Medicity
state: Haryana
city: Mumbai
country: India
facility: Tata Memorial Hospital; Dept of Medical Oncology
state: Maharashtra
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale; S.C. Oncol. Medica Testa-Collo e Sarcoma
state: Campania
city: Lugo
country: Italy
facility: Ospedale Umberto I ASL di Ravenna Presidio Ospedaliero di Lugo
state: Emilia-Romagna
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
state: Lazio
city: Savona
country: Italy
facility: Ospedale Civile; Servizio Oncologia
state: Liguria
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo
state: Lombardia
city: Milano
country: Italy
facility: Asst Santi Paolo E Carlo; Unita Operativa Di Oncologia Medica
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Miyagi
country: Japan
facility: Miyagi Cancer Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Jikei University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
city: Gliwice
country: Poland
facility: Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
city: Warszawa
country: Poland
facility: Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowotworów G?owy i Szyi
city: Coimbra
country: Portugal
facility: IPO de Coimbra; Servico de Oncologia Medica
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
state: Krasnodar
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Main Military Clinical Hospital named after N.N. Burdenko
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: P.A. Herzen Oncological Inst. ; Oncology
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: First MSMU n.a. Sechenov Univercity Hospital 1; Plastic surgery
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.
state: Moskovskaja Oblast
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
state: Sankt Petersburg
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Oncology Dispensary; Chemotherapy
state: Sverdlovsk
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk Regional Oncological Dispancer
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Clinical Oncology Dispensary
city: Tomsk
country: Russian Federation
facility: Tomsk scientific research institute of oncology SO RAMN, PAD; Pathological
city: Cape Town
country: South Africa
facility: Tygerberg Hospital; Oncology Dept
city: George
country: South Africa
facility: GVI Oncology Outeniqua Unit
city: Mayville
country: South Africa
facility: The Oncology Centre; Haematology - Radiation Oncology
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital; Oncology
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Insititut Catala D'Oncologia
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Hematología y Oncología
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Oncologia
city: Taichung
country: Taiwan
facility: China Medical University Hospital;Oncology and Hematology Office Critical Care Center, 14H
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital; Radiation Oncology
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital; Oncology
city: Taipei
country: Taiwan
facility: Division of Hematology and Oncology, Taipei Veterans General Hospital
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital; Oncology
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital; Department of Oncology
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtarslan Oncology Hospital; 2nd Oncology Clinic
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty, Oncology Hospital
city: Kar?iyaka
country: Turkey
facility: ?zmir Medical Point; Oncology
city: Kharkiv
country: Ukraine
facility: Municipal Noncommercial Institution Regional Center of Oncology
state: Kharkiv Governorate
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Oncology Dispensary
state: Podolia Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Oncology Center
city: Kiev
country: Ukraine
facility: Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients
city: Kryvyi Rih
country: Ukraine
facility: ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department
city: Lviv
country: Ukraine
facility: Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary; Medical Oncology Dept
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: The Royal Marsden Hospital, Fulham
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: