HELOISE Study: A Study of Herceptin (Trastuzumab) in Combination With Cisplatin/Capecitabine Chemotherapy in Patients With HER2-Positive Metastatic Gastric or Gastro-Esophageal Junction Cancer

• Duration of overall survival in patients with trastuzumab minimum concentrations Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
• Trastuzumab minimum concentrations (Cmin) on Day 21 of Cycles 1-11 [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
• Progression-free survival in patients with trastuzumab Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
• Objective response rate in patients with trastuzumab Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]

This randomized, open-label, multicenter, international phase IIIb study will compare the efficacy and safety of two Herceptin (trastuzumab) dosing regimens in combination with cisplatin/capecitabine chemotherapy in patients with metastatic gastric or gastro-esophageal junction adenocarcinoma. Patients who have not received prior treatment for metastatic disease will be randomized to receive Herceptin intravenously either an 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks or an 8 mg/kg loading dose followed by 10 mg/kg every 3 weeks. Capecitabine will be administered for 6 cycles at a dose of 800 mg/m2 orally twice on Days 1-14 of each 3-week cycle, cisplatin will be administered intravenously for 6 cycles at a dose of 80 mg/m2 on Day 1 of each 3-week cycle. Anticipated time on study treatment is until disease progression occurs.

• Drug: trastuzumab [Herceptin]
  8 mg/kg iv loading dose, followed by 6 mg/kg iv every 3 weeks
• Drug: trastuzumab [Herceptin]
  8 mg/kg iv loading dose, followed by 10 mg/kg iv every 3 weeks
• Drug: capecitabine
  1600 mg/m2 orally daily Days 1-14 of each 3-week cycle, 6 cycles
• Drug: cisplatin
  80 mg/m2 iv on Day 1 of each 3-week cycle, 6 cycles

• Active Comparator: A
  Interventions:

  • Drug: trastuzumab [Herceptin]
  • Drug: capecitabine
  • Drug: cisplatin
• Experimental: B
  Interventions:

  • Drug: trastuzumab [Herceptin]
  • Drug: capecitabine
  • Drug: cisplatin

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction
• Metastatic disease involving at least 2 organs (at least liver or lung or both)
• HER2-positive primary or metastatic tumor
• Adequate renal function
• Eastern Cooperative Oncology Group (ECOG) performance status 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
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• Current gastrointestinal bleeding
• Other malignancy within the last 5 years, except for carcinoma in situ of the cervix or squamous cell carcinoma of the skin
• History of clinically significant cardio-vascular disease or disorder
• Chronic high-dose corticosteroid therapy
• History or clinical evidence of brain metastases
• Pregnant women
• Active infection with HIV, hepatitis B, hepatitis C, or HIV-positive