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 3TerminatedNCT03452137

Hoffmann-La Roche406 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

406

Conditions

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

Interventions

AtezolizumabDRUG

Atezolizumab intravenous infusion will be administered at a fixed dose on Day 1 of each 21-day cycle for 16 cycles.

PlaceboDRUG

Placebo intravenous infusion will be administered a fixed dose on Day 1 of each 21-day cycle for 16 cycles.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (135)

Outcomes

Primary Outcomes

Investigator-Assessed Event-Free Survival (INV-assessed EFS)

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.

Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Secondary Outcomes

Overall Survival (OS)

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.

Time frame: Randomization to death from any cause (up to 5 years, 5 months)

Independent Review Facility (IRF) Assessed EFS

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.

Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Data from ClinicalTrials.gov

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City of Hope National Medical Center

Duarte, California, United States

University of California San Diego Medical Center; Moores Cancer Center

La Jolla, California, United States

UCLA Hematology/Oncology

Santa Monica, California, United States

Miami Cancer Institute of Baptist Health, Inc.

Miami, Florida, United States

Woodlands Medical Specialists, P.A.

Pensacola, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital

Marietta, Georgia, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Billings Clinic Research Center

Billings, Montana, United States

...and 125 more locations

Percentage of Participants Event-Free for IRF-assessed EFS 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.

Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

Percentage of Participants Event-Free for INV-assessed EFS 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.

Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

Percentage of Participants Event-Free for OS at 2, 3, and 5 Years

Time frame: From randomization to OS event or date last known to be alive 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

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.

Time frame: 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)

Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score

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)

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.

Time frame: From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)

Serum Concentration of Atezolizumab

Time frame: 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

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.

Time frame: Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)