A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: 5-Fluorouracil; Capecitabine; Cisplatin; Pertuzumab; Placebo; Trastuzumab
Intervention description: Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.; Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.; Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.; Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.; Participants will receive placebo (matched to pertuzumab) IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.; Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Intervention MeSH terms: Capecitabine; Fluorouracil; Trastuzumab; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 780.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm
      study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab,
      fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive
      metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be
      randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks
      (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg]
      intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine
      (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue
      to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of
      unacceptable toxicity or withdrawal from the study for another reason.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ

          -  Measurable or evaluable non-measurable disease as assessed by the investigator
             according to RECIST v1.1 criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Life expectancy greater than equal to (>/=) 3 months

        Exclusion Criteria:

          -  Previous cytotoxic chemotherapy for advanced (metastatic) disease

          -  Evidence of disease progression documented within 6 months after completion of prior
             neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ
             adenocarcinoma

          -  Previous treatment with any HER2-directed therapy, at any time, for any duration

          -  Previous exposure to any investigational treatment within 30 days before the first
             dose of study treatment

          -  Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks
             if given as palliation to bone metastases, if recovered from all toxicities)

          -  History or evidence of brain metastases

          -  Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to
             National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version
             4.0 [CTCAEv.4.0])

          -  Residual toxicity resulting from previous therapy (for example, hematologic,
             cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted

          -  Other malignancy (in addition to gastric cancer [GC]) within 5 years before
             enrollment, except for carcinoma in situ of the cervix or squamous or basal cell
             carcinoma of the skin that has been previously treated with curative intent

          -  Inadequate hematologic, renal or liver function

          -  Pregnant or lactating women

          -  History of congestive heart failure of any New York Heart Association (NYHA) criteria

          -  Angina pectoris requiring treatment

          -  Myocardial infarction within the past 6 months before the first dose of study drug

          -  Clinically significant valvular heart disease or uncontrollable high-risk cardiac
             arrhythmia

          -  History or evidence of poorly controlled hypertension

          -  Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)

          -  Any significant uncontrolled intercurrent systemic illness

          -  Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection