A Study of Herceptin (Trastuzumab) in Combination With Cisplatin/Capecitabine Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastric or Gastro-Esophageal Junction Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: Capecitabine; Cisplatin; Herceptin
Intervention description: Capecitabine will be administered at a dose of 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).; Cisplatin will be administered at a dose of 80 mg/m^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).; Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Intervention MeSH terms: Capecitabine; Trastuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 296.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, open-label, multicenter, international Phase IIIb study will compare the
      efficacy and safety of two Herceptin dosing regimens in combination with
      cisplatin/capecitabine chemotherapy in participants with HER2-positive metastatic gastric or
      gastro-esophageal junction adenocarcinoma. Participants who have not received prior treatment
      for metastatic disease will be randomized to receive Herceptin intravenously as either an
      8-milligram per kilogram (mg/kg) loading dose followed by 6 mg/kg every 3 weeks (q3w) as
      standard of care or an 8-mg/kg loading dose followed by 10 mg/kg q3w until disease
      progression. Capecitabine will be administered for 6 cycles at a dose of 800 milligrams per
      meter-squared (mg/m^2) orally twice a day on Days 1 to 14 of each 3-week cycle, and cisplatin
      will be administered intravenously for 6 cycles at a dose of 80 mg/m^2 on Day 1 of each
      3-week cycle. Herceptin will be continued until disease progression occurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction
             with metastatic disease documented to involve at least liver or lung or both

          -  Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease

          -  At least 2 organs involved in metastatic gastric tumor (including at least lung or
             liver or both) in addition to the site of primary tumor, where metastasis in distant
             lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as
             "organs" in this context

          -  HER2-positive primary or metastatic tumor as assessed by central laboratory

          -  Adequate renal function (creatinine clearance greater than equal to (≥) 45 milliliters
             per minute [mL/min])

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 2

        Exclusion Criteria:

          -  Previous chemotherapy for locally advanced or metastatic disease

          -  Prior gastrectomy (partial or total) for the underlying malignant disease under
             investigation

          -  Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent

          -  Residual relevant toxicity resulting from previous therapy

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair
             the ability to administer or absorb capecitabine

          -  Current (significant or uncontrolled) gastrointestinal bleeding

          -  Other malignancy within the last 5 years, except for carcinoma in situ of the cervix
             and basal or squamous cell carcinoma of the skin

          -  History of documented congestive heart failure, angina pectoris requiring medication,
             electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly
             controlled hypertension, clinically significant valvular heart disease, or high-risk
             uncontrollable arrhythmias

          -  Baseline left ventricular ejection fraction (LVEF) less than (<) 50%, documented by
             echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac
             magnetic resonance imaging (MRI)

          -  Chronic or high-dose corticosteroid therapy

          -  History or clinical evidence of brain metastases

          -  Pregnant women

          -  Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C,
             or HIV-seropositive