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

• Pathological complete response rate at time of total mesorectal excision (TME) [ Designated as safety issue: No ]
  

• Radiological response rates after completion of neoadjuvant therapy [ Designated as safety issue: No ]
  
• Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin [ Designated as safety issue: No ]
  
• Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME [ Designated as safety issue: No ]
  
• Postoperative complications, including wound infection, wound dehiscence, and fistula formation [ Designated as safety issue: No ]
  
• Quality of TME as assessed by audit of photographed surgical specimens [ Designated as safety issue: No ]
  
• Rate of abdominoperitoneal excision [ Designated as safety issue: No ]
  
• Rate of permanent defunctioning colostomies [ Designated as safety issue: No ]
  
• Clinical and radiological anastomotic leak rate [ Designated as safety issue: No ]
  
• Progression-free survival and patterns of failure [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Safety [ Designated as safety issue: Yes ]
  
• Quality of life, including long-term bowel function [ Designated as safety issue: No ]
  

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.