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
- Conditions
- Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- Interventions
- Drug: Placebo
- Registration Number
- NCT03452137
- Lead Sponsor
- Hoffmann-La Roche
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 406
Not provided
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab Participants will receive Atezolizumab for 16 cycles, or up to 1 year (whichever occurs first) Placebo Placebo Participants will receive Placebo for 16 cycles, or up to 1 year (whichever occurs first).
- Primary Outcome Measures
Name Time Method Investigator-Assessed Event-Free Survival (INV-assessed EFS) Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years) EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Randomization to death from any cause (up to 5 years, 5 months) OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.
Independent Review Facility (IRF) Assessed EFS Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years) EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years From randomization to OS event or date last known to be alive at 2, 3, and 5 Years OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 2, 3 and 5 years.
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 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) EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score 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) EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome.
Number of Participants With at Least One Adverse Event (AE) From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months) An AE is untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Serum Concentration of Atezolizumab 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) Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days) Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period.
Trial Locations
- Locations (135)
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
🇺🇸Marietta, Georgia, United States
Cleveland Clinic; Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
Faculdade de Medicina do ABC - FMABC
🇧🇷Santo Andre, SP, Brazil
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
CENTRE LEON BERARD; Département d?Hématologie et d?Oncologie
🇫🇷Lyon, France
Hopital Timone Adultes; Oncologie Medicale Et Usp
🇫🇷Marseille, France
Beijing Cancer Hospital
🇨🇳Beijing, China
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Clinique Ste-Elisabeth
🇧🇪Namur, Belgium
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Santa Casa de Misericordia de Salvador
🇧🇷Salvador, BA, Brazil
Miami Cancer Institute of Baptist Health, Inc.
🇺🇸Miami, Florida, United States
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Ospedale Umberto I ASL di Ravenna Presidio Ospedaliero di Lugo
🇮🇹Lugo, Emilia-Romagna, Italy
Universitätsmedizin Rostock, Klinik und Poliklinik für Strahlentherapie; Zentrum für Radiologie
🇩🇪Rostock, Germany
Hospital do Cancer de Pernambuco - HCP
🇧🇷Recife, PE, Brazil
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Peter MacCallum Cancer Center
🇦🇺North Melbourne, Victoria, Australia
Gustave Roussy Cancer Campus; Radiotherapie
🇫🇷VILLEJUIF Cedex, France
Institut Sainte Catherine
🇫🇷Avignon, France
Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde
🇩🇪Freiburg, Germany
Hopital Tenon; Oncologie Radiotherapie
🇫🇷Paris, France
Budapesti Uzsoki Utcai Kórház
ðŸ‡ðŸ‡ºBudapest, Hungary
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Miyagi Cancer Center
🇯🇵Miyagi, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
ICM; Radiotherapie
🇫🇷Montpellier Cedex 5, France
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
🇮🇹Rozzano, Lombardia, Italy
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
🇷🇺Krasnoyarsk, Krasnodar, Russian Federation
Okayama University Hospital
🇯🇵Okayama, Japan
CHU Bordeaux
🇫🇷Pessac, France
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie
🇩🇪Bonn, Germany
Istituto Nazionale Tumori Fondazione G. Pascale; S.C. Oncol. Medica Testa-Collo e Sarcoma
🇮🇹Napoli, Campania, Italy
Shanghai East Hospital
🇨🇳Shanghai, China
Hôpitaux D'Instruction Des Armees Begin
🇫🇷St Mande, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Klinikum d. Uni. München; Campus Großhadern; Klinik und Poliklinik f. Strahlenthera. und Radioonko
🇩🇪München, Germany
Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
ðŸ‡ðŸ‡ºPécs, Hungary
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
The Jikei University Hospital
🇯🇵Tokyo, Japan
Ivano-Frankivsk Regional Oncology Center
🇺🇦Ivano-Frankivsk, Ukraine
Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients
🇺🇦Kiev, Ukraine
Aberdeen Royal Infirmary; Medical Oncology Dept
🇬🇧Aberdeen, United Kingdom
Hospital ClÃnic i Provincial; Servicio de HematologÃa y OncologÃa
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
The Oncology Centre; Haematology - Radiation Oncology
🇿🇦Mayville, South Africa
Sverdlovsk Regional Oncology Dispensary; Chemotherapy
🇷🇺Ekaterinburg, Sverdlovsk, Russian Federation
Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
🇵🇱Gdansk, Poland
Spedali Civili di Brescia
🇮🇹Brescia, Lombardia, Italy
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Tygerberg Hospital; Oncology Dept
🇿🇦Cape Town, South Africa
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, Italy
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Badalona, Barcelona, Spain
BHI of Omsk region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Universitario la Fe; Servicio de Oncologia
🇪🇸Valencia, Spain
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowotworów G?owy i Szyi
🇵🇱Warszawa, Poland
Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy
🇺🇦Lviv, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
?zmir Medical Point; Oncology
🇹🇷Kar?iyaka, Turkey
Tomsk scientific research institute of oncology SO RAMN, PAD; Pathological
🇷🇺Tomsk, Russian Federation
Novosibirsk Regional Oncological Dispancer
🇷🇺Novosibirsk, Russian Federation
Steve Biko Academic Hospital; Oncology
🇿🇦Pretoria, South Africa
Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
🇪🇸Salamanca, Spain
Vinnytsya Regional Clinical Oncology Dispensary
🇺🇦Vinnytsya, Podolia Governorate, Ukraine
The Royal Marsden Hospital, Fulham
🇬🇧London, United Kingdom
GVI Oncology Outeniqua Unit
🇿🇦George, South Africa
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
Gazi University Medical Faculty, Oncology Hospital
🇹🇷Ankara, Turkey
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
China Medical University Hospital;Oncology and Hematology Office Critical Care Center, 14H
🇨🇳Taichung, Taiwan
Tata Memorial Hospital; Dept of Medical Oncology
🇮🇳Mumbai, Maharashtra, India
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
🇮🇹Roma, Lazio, Italy
IPO de Coimbra; Servico de Oncologia Medica
🇵🇹Coimbra, Portugal
IPO do Porto; Servico de Oncologia Medica
🇵🇹Porto, Portugal
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
🇹ðŸ‡Bangkok, Thailand
Ospedale Civile; Servizio Oncologia
🇮🇹Savona, Liguria, Italy
Hospital de Santa Maria; Servico de Oncologia Medica
🇵🇹Lisboa, Portugal
National Taiwan University Hospital; Oncology
🇨🇳Zhongzheng Dist., Taiwan
Division of Hematology and Oncology, Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Taichung Veterans General Hospital; Radiation Oncology
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital; Oncology
🇨🇳Tainan, Taiwan
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
🇹ðŸ‡Bangkok, Thailand
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
Zhejiang Cancer Hospital
🇨🇳Zhejiang, China
Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo
🇮🇹Milano, Lombardia, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
🇮🇹Meldola, Emilia-Romagna, Italy
Asst Santi Paolo E Carlo; Unita Operativa Di Oncologia Medica
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
🇮🇹Firenze, Toscana, Italy
Dr. Abdurrahman Yurtarslan Oncology Hospital; 2nd Oncology Clinic
🇹🇷Ankara, Turkey
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Tokyo Medical and Dental University Hospital
🇯🇵Tokyo, Japan
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
University of California San Diego Medical Center; Moores Cancer Center
🇺🇸La Jolla, California, United States
Adelaide Cancer Centre
🇦🇺Kurralta Park, South Australia, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Orszagos Onkologial Intezet; Onkologiai Osztaly X
ðŸ‡ðŸ‡ºBudapest, Hungary
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Kobe University Hospital
🇯🇵Hyogo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
P.A. Herzen Oncological Inst. ; Oncology
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
First MSMU n.a. Sechenov Univercity Hospital 1; Plastic surgery
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Main Military Clinical Hospital named after N.N. Burdenko
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Insititut Catala D'Oncologia
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Songklanagarind Hospital; Department of Oncology
🇹ðŸ‡Songkhla, Thailand
ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department
🇺🇦Kryvyi Rih, Ukraine
Municipal Noncommercial Institution Regional Center of Oncology
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
🇵🇱Gliwice, Poland
Woodlands Medical Specialists, P.A.
🇺🇸Pensacola, Florida, United States
Billings Clinic Research Center
🇺🇸Billings, Montana, United States
Medanta-The Medicity
🇮🇳Gurgaon, Haryana, India