Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction AdenocarcinomaPhase 3NCT02625623
Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)
A Phase 3 study testing Avelumab, Irinotecan and Paclitaxel in people with Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma and Gastric Cancer Third Line, run by EMD Serono Research & Development Institute, Inc. at 75 sites in 10 countries.
Trial summary
The purpose of this study was 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Gastric Cancer Third Line
- What is being tested?
- Avelumab, Irinotecan and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 371 participants
- Where
- 75 sitesin 10 countries
- Study dates
- 28 Dec 2015to 13 Nov 2019
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
75 sites in 10 countries.
75 sites in 10 countries
United States28 sites
New York Oncology Hematology, P.C. 400 Patroon Creek Blvd, Suite 1
Albany, New York, 12206
Texas Oncology Bedford 1609 Hospital Parkway
Bedford, Texas, 76022
Texas Oncology, P.A. 3410 Worth Street, Suites 300 & 400
Dallas, Texas, 75246
Texas Oncology, P.A. - Denton 3720 South I-35 East
Denton, Texas, 76210
Rocky Mountain Cancer Centers 1800 Williams Street, Suite 100
Denver, Colorado, 80218
Henry Ford Health System 2799 West Grand Boulevard
Detroit, Michigan, 48202
Sanford Roger Maris Cancer Center - Fargo 801 Broadway North Route 1058
Fargo, North Dakota, 58122
Hematology and Oncology Associates of SC, LLC 900 West Faris Rd, 3rd Floor
Greenville, South Carolina, 29605
Ingalls Memorial Hospital One Ingalls Drive, W741
Harvey, Illinois, 60426
Penn State University Milton S. Hershey Medical Center 500 University Drive
Hershey, Pennsylvania, 17033
Oncology Consultants, P.A. 2130 W. Holcombe Blvd. 10th Floor
Houston, Texas, 77030
Southern Nevada Cancer Research Foundation 601 S Rancho Drive
Las Vegas, Nevada, 89106
Texas Oncology, P.A. - McAllen 1901 South 2nd Street
McAllen, Texas, 78503-1298
Metairie Oncologist, LLC Office of Jayne Gurtler MD, Laura Brinz MD, Janet Burroff MD 3939 Houma Blvd, Suite 6
Metairie, Louisiana, 70006
Advanced Medical Specialties 8940 North Kendall Drive, Suite 300E
Miami, Florida, 33176
Minnesota Oncology Hematology, P.A. 910 East 26th Street, Suites 100 and 200
Minneapolis, Minnesota, 55404
Tennessee Oncology 250 20th Ave North
Nashville, Tennessee, 37203
Illinois Cancer Specialists 8915 W. Golf Rd.
Niles, Illinois, 60714
Oncology Specialists, S.C. 1700 Luther Ln, Ste 2200, Park Ridge, IL 60068 7900 Milwaukee Ave, Ste 16
Niles, Illinois, 60714
Ocala Oncology Center, P.L. 433 S.W. 10th Street
Ocala, Florida, 34471
Northwest Cancer Specialists, P.C. 265 N Broadway
Portland, Oregon, 97227
Rocky Mountain Cancer Centers, LLP 3676 Parker Blvd #350
Pueblo, Colorado, 81008
Florida Cancer Specialists 560 Jackson Street, Suite 220
St. Petersburg, Florida, 33705
Scott and White Memorial Hospital and Clinic 2401 South 31st Street
Temple, Texas, 76508
Cotton-O'Neil Clinical Research Center, Hematology and Oncology and Stormont Vail Cancer Center 1414 SW 8th St
Topeka, Kansas, 66604
Texas Oncology, P.A. - Tyler 910 E. Houston St, Suite 100
Tyler, Texas, 75702
Carle Cancer Center 509 W. University Avenue
Urbana, Illinois, 61801
Texas Oncology - Waco 1700 W. Hwy. 6
Waco, Texas, 76712
South Korea10 sites
Kyungpook National University Medical Center
Daegu, 41404
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Chonnam National University Hwasun Hospital
Hwasun-Gun, Jeollanam-do, 58128
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 02841
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
Seoul National Univ Hospital
Seoul, 3080
Australia8 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Box Hill Hospital
Box Hill, Victoria, 3128
Royal Hobart Hospital
Hobart, Tasmania, 7000
Sunshine Hospital
St Albans, Victoria, 3021
Fiona Stanley Hospital
Subiaco, Western Australia, 6008
Border Medical Oncology
Wodonga, Victoria, 3690
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Belgium8 sites
OLV Ziekenhuis
Aalst, 9300
AZ Sint Lucas
Bruges, 8310
ULB Hopital Erasme
Brussels, 1070
Cliniques Universitaires Saint-Luc
Brussels, 1200
UZ Antwerpen
Edegem, 2650
CHC Clinique StJospeh
Liège, 4000
CHU Sart Tilman
Liège, 4000
AZ Turnhout - Campus Sint-Elisabeth
Turnhout, 2300
Spain8 sites
Hospital Univ Vall dHebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital del Mar
Barcelona, 8003
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Clinico San Carlos Hospital
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario la Paz - site 546
Madrid, 28046
Hosp Univer Madrid Sanchinarro
Madrid, 28050
Germany5 sites
Charite Universitaetsmedizin
Berlin, 13353
Universitaetsklinikum Koeln
Cologne, North Rhine-Westphalia, 50937
Schwerpunktpraxis für Haematologie und OnkologieOnkologische Schwerpunktpraxis Eppendorf
Hamburg, 20249
Schwerpunktpraxis für Haematologie und Onkologie
Magdeburg, Saxony-Anhalt, 39104
Leopoldina Krankenhaus
Schweinfurt, 97422
France3 sites
Service d'Oncologie Médicale
Brest, Finistere, 29609
Service d'Hépato-Gastro-Entérologie
La Roche S/ Yon Cedex 9, Vendee, 85925
Centre Oscar Lambret
Lille, 59020
Italy3 sites
Fondazione del Piemonte per l'Oncologia IRCC Candiolo
Candiolo, Torino, 10060
Ospedale San Raffaele
Milan, 20132
A.O.U. Ospedali Riuniti Ancona- Clinica Oncologica
Torrette Di Ancona, Ancona, 60126
Poland1 site
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
Warsaw, 02-781
About this study
Official 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
The purpose of this study was 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.
- Conditions
- Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Gastric Cancer Third Line
- Being tested
- Avelumab, Irinotecan, Paclitaxel, Best Supportive Care (BSC)
- Keywords
- Avelumab, Gastric cancer, Gastroesophageal junction adenocarcinoma
- Medical subject headings
- Recurrence, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Also called MSB0010718C, Anti PD-L1
Avelumab was 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).
IrinotecanDrug
Irinotecan was 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.
PaclitaxelDrug
Paclitaxel was 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.
Best Supportive Care (BSC)Other
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 was administered once every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Physician choice chemotherapy+Best Supportive Care (BSC) | Experimental | Participants received 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. Receives: Drug: Irinotecan; Drug: Paclitaxel; Other: Best Supportive Care (BSC) |
| Avelumab+BSC | Active comparator | Participants received 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. Receives: Drug: Avelumab; Other: Best Supportive Care (BSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization up to 627 days
Secondary outcomes (7)
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.
Measured: From randomization up to 627 days
Best Overall Response (BOR)
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).
Measured: From randomization up to 627 days
Objective Response Rate (ORR)
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.
Measured: From randomization up to 627 days
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.
Measured: Baseline, EOT (up to Week 66)
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)
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.
Measured: Baseline, EOT (up to Week 66)
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)
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.
Measured: Baseline, EOT (up to Week 66)
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)
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.
Measured: Baseline, EOT (up to Week 66)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2015 (estimated)
- Study start28 Dec 2015
- Primary completion14 Sep 2017
- Study completion13 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 371 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02625623
- Sponsor's protocol ID
- EMR 100070-008
- Other IDs
- 2015-003301-42, 2015
- Status last verified
- Oct 2020
- First submitted
- 4 Dec 2015
- Last updated
- 24 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. doi: 10.1093/annonc/mdy264.
PubMed 30052729