RATIONALE: Drugs used in chemotherapy, such as epirubicin, cisplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, and small molecule tyrosine kinase inhibitors, such as lapatinib, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Lapatinib targets a specific growth receptor, HER-2. Chemotherapy together with bevacizumab or lapatinib, in HER-2 positive tumours, may kill more tumor cells. PURPOSE: This randomized phase II/III trial is studying the side effects and how well giving combination chemotherapy together with bevacizumab works compared with combination chemotherapy alone in treating patients with previously untreated stomach cancer, gastroesophageal junction cancer or lower oesophageal cancer that can be removed by surgery. The feasibility study is studying the safety of adding lapatinib to chemotherapy in patients with HER-2 positive previously untreated stomach cancer, gastroesophageal junction cancer or lower oesophageal cancer that can be removed by surgery. The feasibility study will also assess the feasibility of timely HER-2 testing and estimate the HER-2 positivity rate in this patient population.
OBJECTIVES: Primary * Assess the safety and efficacy of neoadjuvant and adjuvant chemotherapy comprising epirubicin hydrochloride, cisplatin, and capecitabine with or without bevacizumab in patients with previously untreated, resectable gastric, gastroesophageal junction or lower oesophageal cancer. * Assess the safety of neoadjuvant and adjuvant chemotherapy comprising epirubicin hydrochloride, cisplatin, and capecitabine with or without lapatinib in patients with HER-2 positive previously untreated, resectable gastric, gastroesophageal junction or lower oesophageal cancer. OUTLINE: This is a multicenter, randomized, open-label, controlled study. Patients are randomized to 1 of 4 treatment arms. * Arm I and II: Patients receive epirubicin hydrochloride IV and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 5-6 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy beginning 6-10 weeks after surgery. * Arm II: Patients receive bevacizumab IV over 30-90 minutes, epirubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 5-8 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy and bevacizumab beginning 6-10 weeks after surgery. Patients then receive maintenance therapy comprising bevacizumab IV over 30-90 minutes on day 1. Maintenance therapy repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. * Arm IV: Patients receive lapatinib orally once daily, epirubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 5-8 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy and lapatinib beginning 6-10 weeks after surgery. Patients then receive maintenance therapy comprising lapatinib orally once daily on days 1-21. Maintenance therapy repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, during treatment, and during the follow-up period. After completion of study treatment, patients are followed at 9, 18, and 27 weeks after the start of course 4, 1 year post surgery, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1063 patients were recruited to the bevacizumab comparison of the study (now closed to recruitment) and 40 patients with HER-2 positive tumours will be recruited into the ST03 feasibility study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,103
7.5mg/kg IV Day 1 of each 21 cycle of chemotherapy (6 cycles) plus day 1 of each maintenance dose every 21 days for 6 doses.
dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
3 cycles of ECX chemotherapy post operatively
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
3 cycles of pre-operative ECX chemotherapy.
1250mg/day Day 1-21 of each cycle of chemotherapy (6 cycles) plus day 1-21 of each maintenance course every 21 days for 6 doses.
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom
RECRUITINGBradford Royal Infirmary
Bradford, England, United Kingdom
ACTIVE_NOT_RECRUITINGBristol Haematology and Oncology Centre
Bristol, England, United Kingdom
RECRUITINGAddenbrooke's Hospital
Cambridge, England, United Kingdom
Safety
Time frame: at the end of phase II and phase III
Efficacy
Time frame: end of trial
Overall survival
Time frame: end of trial
Feasibility
Time frame: end of trial
Treatment-related morbidity
Time frame: end of trial
Response rates to pre-operative treatment
Time frame: at phase II review and at end of trial
Surgical resection rates
Time frame: end of trial
Disease-free survival
Time frame: end of trial
Quality of life
Time frame: end of trial
Cost-effectiveness
Time frame: end of trial
HER-2 Positivity Rate
Time frame: End of trial
Feasibility of centralised HER-2 testing
Time frame: After 60 patients tested and then after 110 patients tested and then at end of trial
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cumberland Infirmary
Carlisle, England, United Kingdom
ACTIVE_NOT_RECRUITINGDoncaster Royal Infirmary
Doncaster, England, United Kingdom
RECRUITINGSt. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom
RECRUITINGHuddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom
RECRUITINGLeeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom
RECRUITINGLincoln County Hospital
Lincoln, England, United Kingdom
ACTIVE_NOT_RECRUITING...and 31 more locations