A Randomised Phase II/III Trial of Peri-Operative Chemotherapy With or Without Bevacizumab in Operable Oesophagogastric Adenocarcinoma and A Feasibility Study Evaluating Lapatinib in HER-2 Positive Oesophagogastric Adenocarcinomas
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 1,100 patients will be accrued for this study and 40 patients
with HER-2 positive tumours recruited into the ST03 feasibility study.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety
at the end of phase II and phase III
Yes
David Cunningham, MD
Study Chair
Royal Marsden NHS Foundation Trust
United Kingdom: Medicines and Healthcare Products Regulatory Agency
CDR0000536013
NCT00450203
October 2007
December 2016
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