Brief Summary
The purpose of this study was to demonstrate superiority of treatment with avelumab versus continuation of first-line chemotherapy.
Brief Title
Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction
Eligibility Criteria
Inclusion Criteria:
* Male or female participants greater than or equal to (\>=) 18 years
* Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
* Estimated life expectancy of more than 12 weeks
* Adequate haematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential
* Highly effective contraception for both male and female participants if the risk of conception exists
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
* Concurrent anticancer treatment or immunosuppressive agents
* Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Tumor shown to be human epidermal growth factor 2 plus (HER2+)
* Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the participant has not fully recovered from the surgery within 4 weeks of enrolment
* Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of participants with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to \<= 10 mg prednisone daily)
* All participants with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
* Prior organ transplantation, including allogeneic stem-cell transplantation
* Significant acute or chronic infections
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
* Persisting toxicity related to prior therapy except alopecia
* Neuropathy Grade \> 3
* Pregnancy or lactation
* Known alcohol or drug abuse
* History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
* Clinically significant (i.e., active) cardiovascular disease
* All other significant diseases might impair the participant's tolerance of study treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
* Vaccination with live or live/attenuated viruses within 55 days of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
* Legal incapacity or limited legal capacity
* Participants will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
* Other protocol defined exclusion criteria could apply
* Male or female participants greater than or equal to (\>=) 18 years
* Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
* Estimated life expectancy of more than 12 weeks
* Adequate haematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential
* Highly effective contraception for both male and female participants if the risk of conception exists
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
* Concurrent anticancer treatment or immunosuppressive agents
* Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Tumor shown to be human epidermal growth factor 2 plus (HER2+)
* Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the participant has not fully recovered from the surgery within 4 weeks of enrolment
* Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of participants with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to \<= 10 mg prednisone daily)
* All participants with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
* Prior organ transplantation, including allogeneic stem-cell transplantation
* Significant acute or chronic infections
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
* Persisting toxicity related to prior therapy except alopecia
* Neuropathy Grade \> 3
* Pregnancy or lactation
* Known alcohol or drug abuse
* History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
* Clinically significant (i.e., active) cardiovascular disease
* All other significant diseases might impair the participant's tolerance of study treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
* Vaccination with live or live/attenuated viruses within 55 days of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
* Legal incapacity or limited legal capacity
* Participants will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
* Other protocol defined exclusion criteria could apply
Inclusion Criteria
Inclusion Criteria:
* Male or female participants greater than or equal to (\>=) 18 years
* Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
* Estimated life expectancy of more than 12 weeks
* Adequate haematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential
* Highly effective contraception for both male and female participants if the risk of conception exists
* Other protocol defined inclusion criteria could apply
* Male or female participants greater than or equal to (\>=) 18 years
* Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
* Estimated life expectancy of more than 12 weeks
* Adequate haematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential
* Highly effective contraception for both male and female participants if the risk of conception exists
* Other protocol defined inclusion criteria could apply
Gender
All
Gender Based
false
Keywords
Avelumab
Cancer
Unresectable
Locally advanced
Metastatic
Adenocarcinoma of the stomach
Gastro-esophageal junction
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02625610
Org Class
Industry
Org Full Name
EMD Serono
Org Study Id
EMR 100070-007
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase III Open-label, Multicenter Trial of Maintenance Therapy With Avelumab (MSB0010718C) Versus Continuation of First-line Chemotherapy in Subjects With Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro-esophageal Junction
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Secondary Ids
Secondary Id
2015-003300-23
Secondary Outcomes
Outcome 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) 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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Progression Free Survival (PFS) by Independent Review Committee (IRC)
Outcome Description
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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Best Overall Response (BOR) by Investigator Assessment
Outcome 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 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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Objective Response Rate (ORR) by Investigator Assessment
Outcome 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.
Outcome 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)
Outcome Measure
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)
Outcome 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.
Outcome 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)
Outcome Measure
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)
Outcome Description
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.
Outcome 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)
Outcome Measure
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)
Outcome Description
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.
Outcome 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)
Outcome Measure
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)
Outcome Description
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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
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)
Outcome Description
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.
Outcome Time Frame
From baseline up to 1276 days
Outcome Measure
Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values
Outcome Description
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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Outcome Description
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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Outcome Description
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.
Outcome Time Frame
From randomization into maintenance phase up to 1276 days
Outcome Measure
Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jennifer Chuy
Investigator Email
jchuy@montefiore.org
Investigator Phone
Categories Mesh Debug
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
NEOPLASM METASTASIS
NEOPLASMS
NEOPLASTIC PROCESSES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
AVELUMAB
OXALIPLATIN
FLUOROURACIL
LEUCOVORIN
CAPECITABINE
COORDINATION COMPLEXES
ORGANIC CHEMICALS
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
FORMYLTETRAHYDROFOLATES
TETRAHYDROFOLATES
FOLIC ACID
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
COENZYMES
ENZYMES AND COENZYMES
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES