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Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02625623
Recruitment Status : Completed
First Posted : December 9, 2015
Results First Posted : October 15, 2018
Last Update Posted : November 24, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric Cancer Third Line
Interventions Drug: Avelumab
Drug: Irinotecan
Drug: Paclitaxel
Other: Best Supportive Care (BSC)
Enrollment 371
Recruitment Details Overall, 459 participants were screened for this study. Of which, 371 participants were randomized into the study.
Pre-assignment Details  
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Period Title: Overall Study
Started 186 185
Treated 177 184
Completed 177 184
Not Completed 9 1
Reason Not Completed
Participants randomized but not treated             9             1
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC Total
Hide Arm/Group Description Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. Total of all reporting groups
Overall Number of Baseline Participants 186 185 371
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all participants who were randomized to study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 186 participants 185 participants 371 participants
60.1  (12.93) 58.8  (11.66) 59.5  (12.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 185 participants 371 participants
Female
59
  31.7%
45
  24.3%
104
  28.0%
Male
127
  68.3%
140
  75.7%
267
  72.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 185 participants 371 participants
Hispanic or Latino
15
   8.1%
15
   8.1%
30
   8.1%
Not Hispanic or Latino
150
  80.6%
153
  82.7%
303
  81.7%
Unknown or Not Reported
21
  11.3%
17
   9.2%
38
  10.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 185 participants 371 participants
White
117
  62.9%
119
  64.3%
236
  63.6%
Black or African American
1
   0.5%
1
   0.5%
2
   0.5%
Asian
47
  25.3%
47
  25.4%
94
  25.3%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Not collected/Missing
19
  10.2%
15
   8.1%
34
   9.2%
Other
2
   1.1%
3
   1.6%
5
   1.3%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS 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 up to 627 days
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to study treatment.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 186 185
Median (95% Confidence Interval)
Unit of Measure: months
5.0
(4.5 to 6.3)
4.6
(3.6 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8078
Comments [Not Specified]
Method Log Rank
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The stratification factor was region (Asia versus non Asia).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.88 to 1.41
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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). 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 up to 627 days
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to study treatment.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 186 185
Median (95% Confidence Interval)
Unit of Measure: months
2.7
(1.81 to 2.83)
1.4
(1.38 to 1.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Log Rank
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The stratification factor was region (Asia versus non Asia).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.73
Confidence Interval (2-Sided) 95%
1.36 to 2.21
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Best Overall Response (BOR)
Hide Description BOR was determined by RECIST v1.1 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 (and not qualifying for CR, PR or SD).
Time Frame From randomization up to 627 days
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to study treatment.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 186 185
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
1
   0.5%
1
   0.5%
Partial response
7
   3.8%
3
   1.6%
Stable disease
62
  33.3%
30
  16.2%
Non-complete response/ Non-progressive disease
12
   6.5%
7
   3.8%
Progressive disease
59
  31.7%
94
  50.8%
Non-evaluable
45
  24.2%
50
  27.0%
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description 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 adjudicated by the Independent Review Committee (IRC). 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 up to 627 days
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized to study treatment.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + SC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 186 185
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.3
(1.9 to 8.3)
2.2
(0.6 to 5.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Physician Choice Chemotherapy + Best Supportive Care (BSC), Avelumab + SC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8764
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The treatment arms were compared by 1-sided CMH test. The stratification factor was region (Asia versus non Asia).
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.709
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)
Hide Description 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, EOT (up to Week 66)
Hide Outcome Measure Data
Hide Analysis Population Description
Health-related quality of life (HRQoL) analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 92 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.103  (0.2113) -0.144  (0.2088)
6.Secondary Outcome
Title Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)
Hide Description 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, EOT (up to Week 66)
Hide Outcome Measure Data
Hide Analysis Population Description
HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment, had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 92 74
Mean (Standard Deviation)
Unit of Measure: millimeter (mm)
-12.3  (19.22) -13.6  (19.76)
7.Secondary Outcome
Title Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)
Hide Description 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, EOT (up to Week 66)
Hide Outcome Measure Data
Hide Analysis Population Description
HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment and had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 92 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
-10.14  (19.914) -15.77  (19.437)
8.Secondary Outcome
Title 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 at End of Treatment (EOT)
Hide Description The 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, EOT (up to Week 66)
Hide Outcome Measure Data
Hide Analysis Population Description
HRQoL analysis set included a subset of the FAS and included FAS participants who met the following criteria: had 1 Baseline HRQoL assessment and had at least 1 post-Baseline HRQoL questionnaire completed. "Number of Participants Analyzed" signifies the number of participants analyzed in this outcome.
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description:
Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
Overall Number of Participants Analyzed 92 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
Dysphagia 7.25  (28.551) 15.32  (29.120)
Pain 8.88  (22.402) 9.23  (21.527)
Reflux 4.59  (20.184) 7.96  (18.347)
Eating Restrictions 9.24  (22.661) 13.29  (21.276)
Anxiety 7.49  (21.860) 6.61  (19.456)
Dry Mouth 15.94  (27.725) 9.01  (28.827)
Tasting 9.42  (25.832) 2.25  (35.897)
Body Image 5.07  (28.787) 4.05  (27.561)
Hair Loss 4.71  (33.546) -13.96  (26.029)
Time Frame From randomization up to 627 days
Adverse Event Reporting Description All participants who received at least 1 dose of study drug (that is, treated participants) were included in safety population.
 
Arm/Group Title Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Hide Arm/Group Description Participants received BSC plus physician's choice chemotherapy. Chemotherapy comprised of one of the following: intravenous (IV) infusion of paclitaxel at a dose of 80 milligrams per meter square (mg/m^2) on Days 1, 8 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity OR irinotecan at a dose of 150 mg/m^2 on Days 1 and 15 of a 4-week treatment cycle until progressive disease or unacceptable toxicity. Participants who were not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion. Participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity along with BSC. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on investigator's discretion.
All-Cause Mortality
Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Affected / at Risk (%) Affected / at Risk (%)
Total   131/177 (74.01%)   142/184 (77.17%) 
Hide Serious Adverse Events
Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Affected / at Risk (%) Affected / at Risk (%)
Total   81/177 (45.76%)   90/184 (48.91%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/177 (1.69%)  5/184 (2.72%) 
Febrile neutropenia * 1  3/177 (1.69%)  0/184 (0.00%) 
Disseminated intravascular coagulation * 1  0/177 (0.00%)  1/184 (0.54%) 
Lymphadenopathy mediastinal * 1  0/177 (0.00%)  1/184 (0.54%) 
Cardiac disorders     
Cardio-respiratory arrest * 1  0/177 (0.00%)  1/184 (0.54%) 
Pericardial effusion * 1  0/177 (0.00%)  1/184 (0.54%) 
Cardiac arrest * 1  1/177 (0.56%)  0/184 (0.00%) 
Tachycardia * 1  1/177 (0.56%)  0/184 (0.00%) 
Endocrine disorders     
Autoimmune hypothyroidism * 1  0/177 (0.00%)  1/184 (0.54%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/177 (0.56%)  6/184 (3.26%) 
Vomiting * 1  1/177 (0.56%)  5/184 (2.72%) 
Intestinal obstruction * 1  1/177 (0.56%)  4/184 (2.17%) 
Ascites * 1  1/177 (0.56%)  3/184 (1.63%) 
Dysphagia * 1  1/177 (0.56%)  3/184 (1.63%) 
Ileus * 1  4/177 (2.26%)  2/184 (1.09%) 
Subileus * 1  3/177 (1.69%)  1/184 (0.54%) 
Diarrhoea * 1  3/177 (1.69%)  0/184 (0.00%) 
Abdominal pain upper * 1  0/177 (0.00%)  2/184 (1.09%) 
Colitis * 1  0/177 (0.00%)  1/184 (0.54%) 
Constipation * 1  1/177 (0.56%)  1/184 (0.54%) 
Duodenal obstruction * 1  0/177 (0.00%)  1/184 (0.54%) 
Intestinal perforation * 1  0/177 (0.00%)  1/184 (0.54%) 
Nausea * 1  2/177 (1.13%)  1/184 (0.54%) 
Small intestinal obstruction * 1  1/177 (0.56%)  1/184 (0.54%) 
Gastric stenosis * 1  1/177 (0.56%)  0/184 (0.00%) 
Haematemesis * 1  1/177 (0.56%)  0/184 (0.00%) 
Haemorrhagic ascites * 1  1/177 (0.56%)  0/184 (0.00%) 
Melaena * 1  1/177 (0.56%)  0/184 (0.00%) 
General disorders     
Disease progression * 1  30/177 (16.95%)  39/184 (21.20%) 
General physical health deterioration * 1  3/177 (1.69%)  11/184 (5.98%) 
Asthenia * 1  2/177 (1.13%)  3/184 (1.63%) 
Pain * 1  0/177 (0.00%)  1/184 (0.54%) 
Pyrexia * 1  1/177 (0.56%)  1/184 (0.54%) 
Chills * 1  1/177 (0.56%)  0/184 (0.00%) 
Condition aggravated * 1  1/177 (0.56%)  0/184 (0.00%) 
Fatigue * 1  1/177 (0.56%)  0/184 (0.00%) 
Multiple organ dysfunction syndrome * 1  1/177 (0.56%)  0/184 (0.00%) 
Oedema peripheral * 1  2/177 (1.13%)  0/184 (0.00%) 
Sudden death * 1  1/177 (0.56%)  0/184 (0.00%) 
Hepatobiliary disorders     
Autoimmune hepatitis * 1  0/177 (0.00%)  1/184 (0.54%) 
Bile duct obstruction * 1  0/177 (0.00%)  1/184 (0.54%) 
Bile duct stone * 1  0/177 (0.00%)  1/184 (0.54%) 
Biliary dilatation * 1  0/177 (0.00%)  1/184 (0.54%) 
Hepatic failure * 1  2/177 (1.13%)  1/184 (0.54%) 
Hepatic function abnormal * 1  0/177 (0.00%)  1/184 (0.54%) 
Jaundice cholestatic * 1  1/177 (0.56%)  1/184 (0.54%) 
Cholangitis * 1  1/177 (0.56%)  0/184 (0.00%) 
Cholecystitis * 1  1/177 (0.56%)  0/184 (0.00%) 
Dilatation intrahepatic duct acquired * 1  1/177 (0.56%)  0/184 (0.00%) 
Infections and infestations     
Pneumonia * 1  2/177 (1.13%)  5/184 (2.72%) 
Sepsis * 1  2/177 (1.13%)  3/184 (1.63%) 
Device related infection * 1  1/177 (0.56%)  2/184 (1.09%) 
Diverticulitis * 1  0/177 (0.00%)  1/184 (0.54%) 
Urinary tract infection * 1  0/177 (0.00%)  1/184 (0.54%) 
Abdominal infection * 1  1/177 (0.56%)  0/184 (0.00%) 
Device related sepsis * 1  1/177 (0.56%)  0/184 (0.00%) 
Empyema * 1  1/177 (0.56%)  0/184 (0.00%) 
Herpes zoster * 1  2/177 (1.13%)  0/184 (0.00%) 
Lung infection * 1  1/177 (0.56%)  0/184 (0.00%) 
Pulmonary sepsis * 1  1/177 (0.56%)  0/184 (0.00%) 
Respiratory tract infection bacterial * 1  1/177 (0.56%)  0/184 (0.00%) 
Septic shock * 1  1/177 (0.56%)  0/184 (0.00%) 
Injury, poisoning and procedural complications     
Hip fracture * 1  0/177 (0.00%)  1/184 (0.54%) 
Infusion related reaction * 1  0/177 (0.00%)  1/184 (0.54%) 
Anastomotic stenosis * 1  1/177 (0.56%)  0/184 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/177 (0.56%)  1/184 (0.54%) 
Aspartate aminotransferase increased * 1  1/177 (0.56%)  1/184 (0.54%) 
Liver function test increased * 1  1/177 (0.56%)  1/184 (0.54%) 
Platelet count decreased * 1  0/177 (0.00%)  1/184 (0.54%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  4/177 (2.26%)  1/184 (0.54%) 
Dehydration * 1  3/177 (1.69%)  1/184 (0.54%) 
Hyponatraemia * 1  0/177 (0.00%)  2/184 (1.09%) 
Malnutrition * 1  1/177 (0.56%)  1/184 (0.54%) 
Hyperuricaemia * 1  1/177 (0.56%)  0/184 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/177 (0.00%)  2/184 (1.09%) 
Exostosis * 1  0/177 (0.00%)  1/184 (0.54%) 
Osteonecrosis * 1  1/177 (0.56%)  0/184 (0.00%) 
Soft tissue disorder * 1  1/177 (0.56%)  0/184 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lymphangiosis carcinomatosa * 1  0/177 (0.00%)  1/184 (0.54%) 
Malignant ascites * 1  0/177 (0.00%)  1/184 (0.54%) 
Malignant neoplasm progression * 1  0/177 (0.00%)  1/184 (0.54%) 
Metastases to central nervous system * 1  0/177 (0.00%)  1/184 (0.54%) 
Metastases to spine * 1  0/177 (0.00%)  1/184 (0.54%) 
Neoplasm swelling * 1  0/177 (0.00%)  1/184 (0.54%) 
Pericarditis malignant * 1  0/177 (0.00%)  1/184 (0.54%) 
Tumour associated fever * 1  0/177 (0.00%)  1/184 (0.54%) 
Tumour pain * 1  2/177 (1.13%)  1/184 (0.54%) 
Neoplasm progression * 1  1/177 (0.56%)  0/184 (0.00%) 
Nervous system disorders     
Dizziness * 1  0/177 (0.00%)  2/184 (1.09%) 
Product Issues     
Device occlusion * 1  0/177 (0.00%)  1/184 (0.54%) 
Renal and urinary disorders     
Hydronephrosis * 1  0/177 (0.00%)  1/184 (0.54%) 
Acute kidney injury * 1  1/177 (0.56%)  0/184 (0.00%) 
Renal failure * 1  1/177 (0.56%)  0/184 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  4/177 (2.26%)  2/184 (1.09%) 
Pneumonia aspiration * 1  1/177 (0.56%)  2/184 (1.09%) 
Pulmonary oedema * 1  0/177 (0.00%)  1/184 (0.54%) 
Respiratory failure * 1  1/177 (0.56%)  1/184 (0.54%) 
Pleural effusion * 1  1/177 (0.56%)  0/184 (0.00%) 
Pulmonary embolism * 1  2/177 (1.13%)  0/184 (0.00%) 
Respiratory distress * 1  1/177 (0.56%)  0/184 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  1/177 (0.56%)  0/184 (0.00%) 
Shock symptom * 1  1/177 (0.56%)  0/184 (0.00%) 
1
Term from vocabulary, MedDRA version 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Physician Choice Chemotherapy + Best Supportive Care (BSC) Avelumab + BSC
Affected / at Risk (%) Affected / at Risk (%)
Total   150/177 (84.75%)   146/184 (79.35%) 
Blood and lymphatic system disorders     
Anaemia * 1  48/177 (27.12%)  30/184 (16.30%) 
Neutropenia * 1  25/177 (14.12%)  0/184 (0.00%) 
Gastrointestinal disorders     
Nausea * 1  61/177 (34.46%)  34/184 (18.48%) 
Vomiting * 1  32/177 (18.08%)  33/184 (17.93%) 
Abdominal pain * 1  31/177 (17.51%)  25/184 (13.59%) 
Diarrhoea * 1  54/177 (30.51%)  24/184 (13.04%) 
Constipation * 1  27/177 (15.25%)  18/184 (9.78%) 
Dysphagia * 1  2/177 (1.13%)  10/184 (5.43%) 
Abdominal pain upper * 1  18/177 (10.17%)  7/184 (3.80%) 
General disorders     
Fatigue * 1  28/177 (15.82%)  28/184 (15.22%) 
Asthenia * 1  35/177 (19.77%)  26/184 (14.13%) 
Pyrexia * 1  30/177 (16.95%)  21/184 (11.41%) 
Chills * 1  3/177 (1.69%)  19/184 (10.33%) 
Oedema peripheral * 1  16/177 (9.04%)  5/184 (2.72%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  3/177 (1.69%)  18/184 (9.78%) 
Investigations     
Aspartate aminotransferase increased * 1  13/177 (7.34%)  16/184 (8.70%) 
Weight decreased * 1  12/177 (6.78%)  16/184 (8.70%) 
Gamma-glutamyltransferase increased * 1  13/177 (7.34%)  15/184 (8.15%) 
Blood alkaline phosphatase increased * 1  10/177 (5.65%)  14/184 (7.61%) 
Alanine aminotransferase increased * 1  13/177 (7.34%)  11/184 (5.98%) 
Neutrophil count decreased * 1  16/177 (9.04%)  0/184 (0.00%) 
White blood cell count decreased * 1  14/177 (7.91%)  0/184 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  37/177 (20.90%)  29/184 (15.76%) 
Dehydration * 1  3/177 (1.69%)  10/184 (5.43%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  6/177 (3.39%)  18/184 (9.78%) 
Nervous system disorders     
Peripheral sensory neuropathy * 1  14/177 (7.91%)  1/184 (0.54%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  10/177 (5.65%)  8/184 (4.35%) 
Dyspnoea * 1  15/177 (8.47%)  7/184 (3.80%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  25/177 (14.12%)  0/184 (0.00%) 
1
Term from vocabulary, MedDRA version 20.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Communication Center
Organization: Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@emdgroup.com
Layout table for additonal information
Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
ClinicalTrials.gov Identifier: NCT02625623    
Other Study ID Numbers: EMR 100070-008
2015-003301-42 ( EudraCT Number )
First Submitted: December 4, 2015
First Posted: December 9, 2015
Results First Submitted: September 10, 2018
Results First Posted: October 15, 2018
Last Update Posted: November 24, 2020