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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02625623




Registration number
NCT02625623
Ethics application status
Date submitted
4/12/2015
Date registered
9/12/2015
Date last updated
23/12/2019

Titles & IDs
Public title
Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)
Scientific title
A Phase III Open-label, Multicenter Trial of Avelumab (MSB0010718C) as a Third-line Treatment of Unresectable, Recurrent, or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Secondary ID [1] 0 0
2015-003301-42
Secondary ID [2] 0 0
EMR 100070-008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma 0 0
Gastric Cancer Third Line 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Paclitaxel
Other interventions - Best Supportive Care (BSC)

Experimental: Physician choice chemotherapy+Best Supportive Care (BSC) - Participants will receive BSC plus physician's choice chemotherapy. Chemotherapy comprises of one of the following: paclitaxel at a dose of 80 milligram per meter square (mg/m^2) on Days 1, 8, and 15 of a 4-week treatment cycle until confirmed 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 confirmed progressive disease or unacceptable toxicity. Participants who are not deemed eligible to receive paclitaxel or irinotecan at the dose and schedule specified above receive BSC alone once every 3 weeks. BSC is defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and is based on investigator's discretion.

Active Comparator: Avelumab+BSC - Participants will receive avelumab as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with BSC. BSC is defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and is based on investigator's discretion.


Treatment: Drugs: Avelumab
Avelumab will be administered as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with best supportive care (BSC).

Treatment: Drugs: Irinotecan
Irinotecan will be administered at a dose of 150 mg/m ^2 on Day 1 and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered at a dose of 80 mg/m^2 on Day 1, 8, and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.

Other interventions: Best Supportive Care (BSC)
BSC is defined as treatment administered with the intent to maximize Quality of life without a specific antineoplastic regimen and is based on investigator's discretion. BSC will be administered once every 3 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - 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.
Timepoint [1] 0 0
From randomization up to data cutoff (assessed up to 627 days)
Secondary outcome [1] 0 0
Progression Free Survival (PFS) - 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.
Timepoint [1] 0 0
From randomization up to data cutoff (assessed up to 627 days)
Secondary outcome [2] 0 0
Best Overall Response (BOR) - BOR determined by RECIST 1.1 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 percent (%) 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 = progression <= 12 weeks after date of randomization (and not qualifying for CR, PR or SD).
Timepoint [2] 0 0
From randomization up to data cutoff (assessed up to 627 days)
Secondary outcome [3] 0 0
Objective Response Rate (ORR) - The ORR defined as the percentage of all randomized participants with a confirmed BOR of PR or CR according to RECIST v1.1 and as adjudicated by the IRC.
Timepoint [3] 0 0
From randomization up to data cutoff (assessed up to 627 days)
Secondary outcome [4] 0 0
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) - 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.
Timepoint [4] 0 0
Baseline, EOT (up to Week 66)
Secondary outcome [5] 0 0
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at EOT - 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.
Timepoint [5] 0 0
Baseline, EOT (up to Week 66)
Secondary outcome [6] 0 0
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 EOT - 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.
Timepoint [6] 0 0
Baseline, EOT (up to Week 66)
Secondary outcome [7] 0 0
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 EOT - 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.
Timepoint [7] 0 0
Baseline, EOT (up to Week 66)

Eligibility
Key inclusion criteria
- Male or female subjects aged greater than or equal to (>=) 18 years

- Subjects with histologically confirmed recurrent unresectable, recurrent locally
advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction
(GEJ)

- Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor
tissue

- Subjects must have received 2 prior courses of systemic treatment for unresectable,
recurrent, locally advanced or metastatic gastric cancer, and must have progressed
after the second line

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial
entry

- Adequate hematological, 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 subjects if the risk of
conception exists

Other protocol defined inclusion criteria could apply
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy with any antibody or drug targeting T-cell coregulatory proteins

- Concurrent anticancer treatment

- Major surgery

- Subjects receiving immunosuppressive agents (such as steroids) for any reason should
be tapered off these drugs before initiation of the trial treatment (with the
exception of subjects with adrenal insufficiency, who may continue corticosteroids at
physiologic replacement dose, equivalent to less than [<] 10 mg prednisone daily).

- All subjects with brain metastases, except those meeting the following criteria: a.
Brain metastases have been treated locally, 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 of grade >2 related to prior therapy except neuropathy and
alopecia

- Neuropathy Grade greater than or equal (>=) 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 subject's tolerance of trial treatment

- Any psychiatric condition that would prohibit the understanding or rendering of
informed consent and that would limit compliance with study requirements

- Vaccination within 4 weeks of the first dose of avelumab and while on trial is
prohibited except for administration of inactivated vaccines

- Legal incapacity or limited legal capacity

- Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy
if administration of their chemotherapy would be inconsistent with the current local
labeling (for example, in regard to contraindications, warnings/precautions, or
special provisions) for that chemotherapy. Investigators should check updated labeling
via relevant websites before randomization

- Subjects should start treatment administration within 28 days after signing the
informed consent form (ICF). Treatment administration will start within 4 days after
the randomization call

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Sunshine Hospital - St. Albans
Recruitment hospital [7] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [8] 0 0
Fiona Stanley Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3021 - St. Albans
Recruitment postcode(s) [7] 0 0
3690 - Wodonga
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
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United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Dakota
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Belgium
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Aalst
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Belgium
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Brugge
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Belgium
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Bruxelles
Country [19] 0 0
Belgium
State/province [19] 0 0
Edegem
Country [20] 0 0
Belgium
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Liege
Country [21] 0 0
Belgium
State/province [21] 0 0
Liège
Country [22] 0 0
Belgium
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Turnhout
Country [23] 0 0
Czechia
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Benesov
Country [24] 0 0
France
State/province [24] 0 0
Finistere
Country [25] 0 0
France
State/province [25] 0 0
Vendee
Country [26] 0 0
France
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Lille
Country [27] 0 0
Germany
State/province [27] 0 0
Nordrhein Westfalen
Country [28] 0 0
Germany
State/province [28] 0 0
Sachsen Anhalt
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Schweinfurt
Country [32] 0 0
Italy
State/province [32] 0 0
Ancona
Country [33] 0 0
Italy
State/province [33] 0 0
Torino
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
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Korea, Republic of
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Gyeonggi-Do
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Jeollanam-Do
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Poland
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Warszawa
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Spain
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Barcelona
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Spain
State/province [42] 0 0
Barselona
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to demonstrate superiority of treatment with avelumab plus best
supportive care (BSC) versus physician's choice (chosen from a pre-specified list of
therapeutic options) plus BSC.
Trial website
https://clinicaltrials.gov/show/NCT02625623
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications