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

Phase 3

Terminated

Conditions: Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Interventions: Drug: Atezolizumab
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

Inclusion Criteria

Not provided

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 & 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.
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.
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.
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.
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)

Trial Locations

Locations (135): City of Hope National Medical Center
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Duarte, California, United States
University of California San Diego Medical Center; Moores Cancer Center
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La Jolla, California, United States
UCLA Hematology/Oncology
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Santa Monica, California, United States
Miami Cancer Institute of Baptist Health, Inc.
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Miami, Florida, United States
Woodlands Medical Specialists, P.A.
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Pensacola, Florida, United States
Winship Cancer Institute of Emory University
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Atlanta, Georgia, United States
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
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Marietta, Georgia, United States
Cancer Center of Kansas
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Wichita, Kansas, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States
Billings Clinic Research Center
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Billings, Montana, United States
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City of Hope National Medical Center
🇺🇸Duarte, California, United States