Clinical trial NCT02625623: Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric Cancer Third Line
Keywords: Avelumab
Gastric cancer
Gastroesophageal junction adenocarcinoma
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2015-12-09
Enrollment: 371
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization up to 627 days
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization up to 627 days
measure: Best Overall Response (BOR)
timeFrame: From randomization up to 627 days
measure: Objective Response Rate (ORR)
timeFrame: From randomization up to 627 days
measure: 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)
timeFrame: Baseline, EOT (up to Week 66)
measure: 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)
timeFrame: Baseline, EOT (up to Week 66)
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 at End of Treatment (EOT)
timeFrame: Baseline, EOT (up to Week 66)
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 at End of Treatment (EOT)
timeFrame: Baseline, EOT (up to Week 66)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers 1800 Williams Street, Suite 100
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers, LLP 3676 Parker Blvd #350
state: Colorado
city: Miami
country: United States
facility: Advanced Medical Specialties 8940 North Kendall Drive, Suite 300E
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center, P.L. 433 S.W. 10th Street
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists 560 Jackson Street, Suite 220
state: Florida
city: Harvey
country: United States
facility: Ingalls Memorial Hospital One Ingalls Drive, W741
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists 8915 W. Golf Rd.
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists, S.C. 1700 Luther Ln, Ste 2200, Park Ridge, IL 60068 7900 Milwaukee Ave, Ste 16
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center 509 W. University Avenue
state: Illinois
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Hematology and Oncology and Stormont Vail Cancer Center 1414 SW 8th St
state: Kansas
city: Metairie
country: United States
facility: Metairie Oncologist, LLC Office of Jayne Gurtler MD, Laura Brinz MD, Janet Burroff MD 3939 Houma Blvd, Suite 6
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System 2799 West Grand Boulevard
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A. 910 East 26th Street, Suites 100 and 200
state: Minnesota
city: Las Vegas
country: United States
facility: Southern Nevada Cancer Research Foundation 601 S Rancho Drive
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. 400 Patroon Creek Blvd, Suite 1
state: New York
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center - Fargo 801 Broadway North Route 1058
state: North Dakota
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C. 265 N Broadway
state: Oregon
city: Hershey
country: United States
facility: Penn State University Milton S. Hershey Medical Center 500 University Drive
state: Pennsylvania
city: Greenville
country: United States
facility: Hematology and Oncology Associates of SC, LLC 900 West Faris Rd, 3rd Floor
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology 250 20th Ave North
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology Bedford 1609 Hospital Parkway
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. 3410 Worth Street, Suites 300 & 400
state: Texas
city: Denton
country: United States
facility: Texas Oncology, P.A. - Denton 3720 South I-35 East
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A. 2130 W. Holcombe Blvd. 10th Floor
state: Texas
city: McAllen
country: United States
facility: Texas Oncology, P.A. - McAllen 1901 South 2nd Street
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital and Clinic 2401 South 31st Street
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler 910 E. Houston St, Suite 100
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Waco 1700 W. Hwy. 6
state: Texas
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: St. Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Subiaco
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Aalst
country: Belgium
facility: OLV Ziekenhuis
city: Brugge
country: Belgium
facility: AZ Sint Lucas
city: Bruxelles
country: Belgium
facility: ULB Hopital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Liege
country: Belgium
facility: CHC Clinique StJospeh
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Turnhout
country: Belgium
facility: AZ Turnhout - Campus Sint-Elisabeth
city: Benesov
country: Czechia
facility: Nemocnice Rudolfa a Stefanie Benesov, a. s.
city: Brest Cedex
country: France
facility: Service d'Oncologie Médicale
state: Finistere
city: La Roche S/ Yon Cedex 9
country: France
facility: Service d'Hépato-Gastro-Entérologie
state: Vendee
city: Lille
country: France
facility: Centre Oscar Lambret
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein Westfalen
city: Magdeburg
country: Germany
facility: Schwerpunktpraxis für Haematologie und Onkologie
state: Sachsen Anhalt
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin
city: Hamburg
country: Germany
facility: Schwerpunktpraxis für Haematologie und OnkologieOnkologische Schwerpunktpraxis Eppendorf
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus
city: Torrette Di Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti Ancona- Clinica Oncologica
state: Ancona
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia IRCC Candiolo
state: Torino
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-Do
city: Seongnam-Si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Hwasun-Gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-Do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National Univ Hospital
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
city: Barcelona
country: Spain
facility: Hospital Univ Vall dHebron
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barselona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinico San Carlos Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario la Paz - site 546
city: Madrid
country: Spain
facility: Hosp Univer Madrid Sanchinarro
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: 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.