ToGA Study – A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer

This parallel, randomized, open-label, multi-centre study will evaluate the effect on overall survival of trastuzumab (Herceptin) in combination with a chemotherapy compared to the chemotherapy alone in patients with HER2-positive advanced gastric cancer. Trastuzumab (Herceptin) will be administered as intravenous infusion of 6 mg/kg (loading dose 8 mg/kg) every 3 weeks. The chemotherapy consists of a combination of 6 cycles of fluorouracil (800 mg/m2/day intravenous infusion every 3 weeks) and cisplatin (80 mg/m2 intravenous infusion every 3 weeks), or capecitabine (Xeloda, 1000 mg/m2 po twice daily for 14 days every 3 weeks) and cisplatin (80 mg/m2 intravenous infusion every 3 weeks). Treatment with trastuzumab (Herceptin) will continue until disease progression. The target sample size is 300-600 patients.

Official Title

A Randomized, Open-label Study of the Effect of First-line Herceptin in Combination With a Fluoropyrimidine and Cisplatin Versus Chemotherapy Alone on Overall Survival in Patients With HER2-positive Advanced Gastric Cancer

Conditions

• Gastric cancer

Study Type

Interventional

Study Design

Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Further Details

Primary Outcome Measures:

• Overall survival
  [ Time Frame: Through study completion ]
  [ Designated as safety issue: No ]

Secondary Outcome Measures:

• Progression-free survival, time to progression
  [ Time Frame: Tumor assessments: every 6 weeks ]
  [ Designated as safety issue: No ]
• Overall response rate, clinical benefit rate, duration of response
  [ Time Frame: Tumor assessments: every 6 weeks ]
  [ Designated as safety issue: No ]
• Safety: AEs, laboratory parameters, vital signs, LVEF, creatinine clearance
  [ Time Frame: AEs: throughout study, laboratory parameters, vital signs, creatinine clearance: 1x every cycle, LVEF: every 12 weeks ][ Designated as safety issue: No ]

Arms	Assigned Interventions
1: Experimental	Drug: trastuzumab loading dose 8 mg/kg, 6 mg/kg intravenous infusion every 3 weeks  Drug: fluorouracil  800 mg/m2/day intravenous infusion every 3 weeks for 6 cycles Drug: cisplatin 80 mg/m2 intravenous infusion every 3 weeks for 6 cycles Drug: capecitabine 1000 mg/m2 po twice daily for 14 days every 3 weeks for cycles
2: Active Comparator	Drug: fluorouracil 800 mg/m2/day intravenous infusion every 3 weeks for 6 cycles Drug: cisplatin 80 mg/m2 intravenous infusion every 3 weeks for 6 cycles Drug: capecitabine 1000 mg/m2 po twice daily for 14 days every 3 weeks for 6 cycles

Study Start

September 2005 – December 2009

Eligibility & Criteria

• Ages Eligible for Study: 18 Years and older
• Genders Eligible for Study: Both
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients >=18 years of age
• Inoperable locally advanced, recurrent, and/or metastatic cancer of the stomach or gastro-esophageal junction
• Adenocarcinoma
• HER2-positive tumors

Exclusion Criteria:

• Previous chemotherapy for advanced/metastatic disease
• Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome
• History of cardiac disease
• Dyspnoea at rest, due to complications of advanced malignancy or other disease, or patients who require supportive oxygen therapy

Total Enrolment

594

Contact Details

Australia

Adelaide, South Australia, 5011
Box Hill, Victoria, 3128
Brisbane, Queensland, 4101
Kurralta Park, South Australia, 5037
Perth, Western Australia, 6008
Sydney, New South Wales, 2217