NCT00450203

Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer

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 and (in Selected Centres) MRI and PET/CT Sub-studies

• Status: Unknown
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,103 (estimated)
• Sponsor: Professor David Cunningham · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Oesophagogastric Cancer

Interventions

Type	Name	Description
BIOLOGICAL	bevacizumab	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.
DRUG	capecitabine	dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
DRUG	cisplatin	60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
DRUG	Epirubicin	50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
PROCEDURE	adjuvant therapy	3 cycles of ECX chemotherapy post operatively
PROCEDURE	conventional surgery	Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
PROCEDURE	neoadjuvant therapy	3 cycles of pre-operative ECX chemotherapy.
DRUG	Lapatinib	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.

Timeline

• Start date: 2007-10-01
• Primary completion: 2017-12-01
• Completion: 2017-12-01
• First posted: 2007-03-22
• Last updated: 2016-12-01

Locations

41 sites across 1 country: United Kingdom