The purpose of this study was to demonstrate superiority of treatment with avelumab versus continuation of first-line chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
499
Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks.
Induction Phase: Oxaliplatin was administered at a dose of 85 mg per square meter (mg/m\^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m\^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Induction Phase: 5-Fluorouracil was administered at a dose of 2600 mg/m\^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m\^2 IV push on Day 1 and 2400 mg/m\^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Overall Survival (OS)
Overall Survival was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.
Time frame: From randomization into maintenance phase up to 1276 days
Progression Free Survival (PFS) by Independent Review Committee (IRC)
The PFS time was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurs first). PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as per IRC. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: From randomization into maintenance phase up to 1276 days
Best Overall Response (BOR) by Investigator Assessment
BOR was determined by RECIST v1.1 per Investigator assessment and defined as best-confirmed response of any of following: complete response (CR), partial response (PR), stable disease (SD) and PD recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in SLD of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions. PR or CR confirmed at a subsequent tumor assessment, not sooner than 5 weeks after initial documentation or at an assessment later than the next assessment after the initial documentation of PR or CR. SD confirmed at least 6 weeks after randomization. Confirmed PD equal to progression \<=2 weeks after date of randomization.
Time frame: From randomization into maintenance phase up to 1276 days
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Induction Phase: Leucovorin was administered at a dose of 200 mg/m\^2 IV (or) Leucovorin 400 mg/m\^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Induction Phase: Capecitabine was administered at a dose of 1000 mg/m\^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase every 3 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.
Treatment administered with the intent to maximize Quality of Life (QoL) without a specific antineoplastic regimen. These may include for example antibiotics, analgesics, antiemetics, thoracentesis, paracentesis, blood transfusions, nutritional support (including jejunostomy), and focal external-beam radiation for control of pain, cough, dyspnea, or bleeding. Best supportive care were administered per institutional guidelines and participants were visit the clinic every 3 weeks.
Induction Phase: Oxaliplatin will be administered at a dose of 85 mg per square meter (mg/m\^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m\^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks.
Induction Phase: 5-Fluorouracil will be administered at a dose of 2600 mg/m\^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m\^2 IV push on Day 1 and 2400 mg/m\^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks.
Induction Phase: Leucovorin will be administered at a dose of 200 mg/m\^2 IV (or) Leucovorin 400 mg/m\^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.
Induction Phase: Capecitabine will be administered at a dose of 1000 mg/m\^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.
Comprehensive Blood & Cancer Center
Bakersfield, California, United States
Virginia Crosson Cancer Center
Fullerton, California, United States
UCLA Medical Center
Los Angeles, California, United States
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, United States
Sansum Clinic
Santa Barbara, California, United States
Trio - Central Coast Medical Oncology Corporation
Santa Maria, California, United States
Norwalk Hospital
Norwalk, Connecticut, United States
UF Health Cancer Center Orlando
Orlando, Florida, United States
Memorial West Cancer Institute
Pembroke Pines, Florida, United States
University of South Florida - Parent
Tampa, Florida, United States
...and 190 more locations
Objective Response Rate (ORR) by Investigator Assessment
The ORR defined as the percentage of all randomized participants with a confirmed best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1 and as per Investigator assessment. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
Time frame: From randomization into maintenance phase up to 1276 days
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score up to Safety Follow-up (Up to 152.3 Weeks)
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall composite health state index score, with scores ranging from -0.594 to 1. A higher score indicates better health state.
Time frame: Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Change From Baseline in European Quality of Life 5-dimensions Health Outcome Questionnaire Through Visual Analogue Scale up to Safety Follow-up (Up to 152.3 Weeks)
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
Time frame: Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score up to Safety Follow-up (Up to 152.3 Weeks)
European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time frame: Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22 ) Questionnaire Scores up to Safety Follow-up (Up to 152.3 Weeks)
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22 ) supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Time frame: Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks)
Maintenance Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Time frame: From randomization into maintenance phase up to 1276 days
Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values
Blood samples were collected for the analysis of following hematology parameters: lymphocyte count, neutrophil count, white blood cells, platelet count, lipase, serum amylase, creatinine phosphokinase and creatinine. The hematology parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case (Grade 4) post Baseline is presented. Only those participants with increase to grade 4 have been presented.
Time frame: From baseline up to 1276 days
Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Vital signs assessment included Systolic blood pressure (SBP), Diastolic blood pressure (DBP) and Pulse Rate (PR). Number of Participants with any potentially clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.
Time frame: From randomization into maintenance phase up to 1276 days
Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
ECG parameters included heart rate, pulse rate intervals, QRS interval, QT interval corrected based on Fridericia's formula (QTcF) intervals and QTcB intervals. Clinical significance was determined by the investigator. Number of participants with potentially clinically significant ECG abnormalities were reported.
Time frame: From randomization into maintenance phase up to 1276 days
Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1
ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with shift in ECOG PS Score to 1 or Higher Than 1 were reported.
Time frame: From randomization into maintenance phase up to 1276 days