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

NCT ID: NCT02625623

Last Updated: 2020-11-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 371 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-28
• Study Completion Date: 2019-11-13

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.

Conditions

Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma; Gastric Cancer Third Line

Keywords

Avelumab; Gastric cancer; Gastroesophageal junction adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Physician choice chemotherapy+Best Supportive Care (BSC)

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.

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

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.

Paclitaxel

Intervention Type: DRUG

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)

Intervention Type: 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.

Avelumab+BSC

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.

Group Type: ACTIVE_COMPARATOR

Avelumab

Intervention Type: DRUG

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).

Best Supportive Care (BSC)

Intervention Type: 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.

Interventions

Avelumab

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).

Intervention Type: DRUG

Irinotecan

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.

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

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 was administered once every 3 weeks.

Intervention Type: OTHER

Other Intervention Names

MSB0010718C; Anti PD-L1

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Rocky Mountain Cancer Centers 1800 Williams Street, Suite 100

Denver, Colorado, United States

Rocky Mountain Cancer Centers, LLP 3676 Parker Blvd #350

Pueblo, Colorado, United States

Advanced Medical Specialties 8940 North Kendall Drive, Suite 300E

Miami, Florida, United States

Ocala Oncology Center, P.L. 433 S.W. 10th Street

Ocala, Florida, United States

Florida Cancer Specialists 560 Jackson Street, Suite 220

St. Petersburg, Florida, United States

Ingalls Memorial Hospital One Ingalls Drive, W741

Harvey, Illinois, United States

Illinois Cancer Specialists 8915 W. Golf Rd.

Niles, Illinois, United States

Oncology Specialists, S.C. 1700 Luther Ln, Ste 2200, Park Ridge, IL 60068 7900 Milwaukee Ave, Ste 16

Niles, Illinois, United States

Carle Cancer Center 509 W. University Avenue

Urbana, Illinois, United States

Cotton-O'Neil Clinical Research Center, Hematology and Oncology and Stormont Vail Cancer Center 1414 SW 8th St

Topeka, Kansas, United States

Metairie Oncologist, LLC Office of Jayne Gurtler MD, Laura Brinz MD, Janet Burroff MD 3939 Houma Blvd, Suite 6

Metairie, Louisiana, United States

Henry Ford Health System 2799 West Grand Boulevard

Detroit, Michigan, United States

Minnesota Oncology Hematology, P.A. 910 East 26th Street, Suites 100 and 200

Minneapolis, Minnesota, United States

Southern Nevada Cancer Research Foundation 601 S Rancho Drive

Las Vegas, Nevada, United States

New York Oncology Hematology, P.C. 400 Patroon Creek Blvd, Suite 1

Albany, New York, United States

Sanford Roger Maris Cancer Center - Fargo 801 Broadway North Route 1058

Fargo, North Dakota, United States

Northwest Cancer Specialists, P.C. 265 N Broadway

Portland, Oregon, United States

Penn State University Milton S. Hershey Medical Center 500 University Drive

Hershey, Pennsylvania, United States

Hematology and Oncology Associates of SC, LLC 900 West Faris Rd, 3rd Floor

Greenville, South Carolina, United States

Tennessee Oncology 250 20th Ave North

Nashville, Tennessee, United States

Texas Oncology Bedford 1609 Hospital Parkway

Bedford, Texas, United States

Texas Oncology, P.A. 3410 Worth Street, Suites 300 & 400

Dallas, Texas, United States

Texas Oncology, P.A. - Denton 3720 South I-35 East

Denton, Texas, United States

Oncology Consultants, P.A. 2130 W. Holcombe Blvd. 10th Floor

Houston, Texas, United States

Texas Oncology, P.A. - McAllen 1901 South 2nd Street

McAllen, Texas, United States

Scott and White Memorial Hospital and Clinic 2401 South 31st Street

Temple, Texas, United States

Texas Oncology, P.A. - Tyler 910 E. Houston St, Suite 100

Tyler, Texas, United States

Texas Oncology - Waco 1700 W. Hwy. 6

Waco, Texas, United States

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Sunshine Hospital

St Albans, Victoria, Australia

Border Medical Oncology

Wodonga, Victoria, Australia

Fiona Stanley Hospital

Subiaco, Western Australia, Australia

OLV Ziekenhuis

Aalst, , Belgium

AZ Sint Lucas

Bruges, , Belgium

ULB Hopital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

CHC Clinique StJospeh

Liège, , Belgium

CHU Sart Tilman

Liège, , Belgium

AZ Turnhout - Campus Sint-Elisabeth

Turnhout, , Belgium

Nemocnice Rudolfa a Stefanie Benesov, a. s.

Benešov, , Czechia

Service d'Oncologie Médicale

Brest, Finistere, France

Service d'Hépato-Gastro-Entérologie

La Roche S/ Yon Cedex 9, Vendee, France

Centre Oscar Lambret

Lille, , France

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, Germany

Schwerpunktpraxis für Haematologie und Onkologie

Magdeburg, Saxony-Anhalt, Germany

Charite Universitaetsmedizin

Berlin, , Germany

Schwerpunktpraxis für Haematologie und OnkologieOnkologische Schwerpunktpraxis Eppendorf

Hamburg, , Germany

Leopoldina Krankenhaus

Schweinfurt, , Germany

A.O.U. Ospedali Riuniti Ancona- Clinica Oncologica

Torrette Di Ancona, Ancona, Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Ospedale San Raffaele

Milan, , Italy

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, , Poland

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Chonnam National University Hwasun Hospital

Hwasun-Gun, Jeollanam-do, South Korea

Kyungpook National University Medical Center

Daegu, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Seoul National Univ Hospital

Seoul, , South Korea

Hospital Univ Vall dHebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Clinico San Carlos Hospital

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario la Paz - site 546

Madrid, , Spain

Hosp Univer Madrid Sanchinarro

Madrid, , Spain

Countries

United States; Australia; Belgium; Czechia; France; Germany; Italy; Poland; South Korea; Spain

References

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.

Reference Type: RESULT

PMID: 30052729 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=EMR%20100070-008

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

2015-003301-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 100070-008

Identifier Type: -

Identifier Source: org_study_id