Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)
Condition: Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction
MeSH terms: Adenocarcinoma
Intervention: Avelumab; Oxaliplatin; 5-Fluorouracil; Leucovorin; Capecitabine; Best supportive care; Oxaliplatin; 5-Fluorouracil; Leucovorin; Capecitabine
Intervention description: Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks.; Induction Phase: Oxaliplatin was administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks.
Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.; Induction Phase: 5-Fluorouracil was administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.; Induction Phase: Leucovorin was administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.
Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.; Induction Phase: Capecitabine was administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.
Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase every 3 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation.; Treatment administered with the intent to maximize Quality of Life (QoL) without a specific antineoplastic regimen. These may include for example antibiotics, analgesics, antiemetics, thoracentesis, paracentesis, blood transfusions, nutritional support (including jejunostomy), and focal external-beam radiation for control of pain, cough, dyspnea, or bleeding. Best supportive care were administered per institutional guidelines and participants were visit the clinic every 3 weeks.; Induction Phase: Oxaliplatin will be administered at a dose of 85 mg per square meter (mg/m^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks.; Induction Phase: 5-Fluorouracil will be administered at a dose of 2600 mg/m^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m^2 IV push on Day 1 and 2400 mg/m^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks.; Induction Phase: Leucovorin will be administered at a dose of 200 mg/m^2 IV (or) Leucovorin 400 mg/m^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks.; Induction Phase: Capecitabine will be administered at a dose of 1000 mg/m^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks.
Intervention MeSH terms: Leucovorin; Capecitabine; Fluorouracil; Oxaliplatin; Avelumab; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 499.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avelumab; Cancer; Unresectable; Locally advanced; Metastatic; Adenocarcinoma of the stomach; Gastro-esophageal junction

Summary:

      The purpose of this study was to demonstrate superiority of treatment with avelumab versus
      continuation of first-line chemotherapy.
    

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