NCT00383695

Oxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer

A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 164 (estimated)
• Sponsor: Royal Marsden NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, 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. Giving chemotherapy and radiation therapy with or without cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving oxaliplatin, capecitabine, and radiation therapy is more effective with or without cetuximab when given before surgery in treating rectal cancer. PURPOSE: This randomized phase II trial is studying oxaliplatin, capecitabine, and radiation therapy to compare how well they work with or without cetuximab in treating patients undergoing surgery for high-risk rectal cancer.

Detailed description

OBJECTIVES: * Compare the pathological complete response rate at total mesorectal excision in patients with high-risk rectal cancer treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and radiotherapy with or without cetuximab. OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to participating center and presence of T4 disease (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: * Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77. * Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days 85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine twice daily on days 85-126. * Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo total mesorectal excision (TME). * Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77. * Arm II: * Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. * Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1 hour on days 85, 92, 99, 106, 113, and 120. * Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo TME as in arm I. * Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed periodically. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years. PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	cetuximab
DRUG	capecitabine
DRUG	oxaliplatin
PROCEDURE	adjuvant therapy
PROCEDURE	conventional surgery
PROCEDURE	neoadjuvant therapy
RADIATION	radiation therapy

Timeline

• Start date: 2005-09-01
• First posted: 2006-10-03
• Last updated: 2010-01-13

Locations

13 sites across 3 countries: Spain, Sweden, United Kingdom