IXO (Irinotecan, Xeloda, Oxaliplatin) in Rectal Cancer

A Phase II Trial of Neoadjuvant IXO Regimen (Irinotecan, Capecitabine [Xeloda], Oxaliplatin) Followed by Combined Modality Capecitabine and Radiation for Locally Resectable Advanced Rectal Cancer

This is a prospective open label single-arm, single-institution phase II clinical trial to test the efficacy of neoadjuvant treatment with IXO (Irinotecan, Capecitabine [Xeloda], Oxaliplatin) followed by chemoradiotherapy and resection in patients with resectable non-metastatic primary rectal cancer of stage cT3-T4 N0-N2.

Inclusion Criteria:

General

• Pathologically confirmed rectal adenocarcinoma
• T3 or T4 or N1 (node ≥1 cm on short axis) adenocarcinoma of the rectum.
• ECOG performance status equal or less than 1
• Male and female patients, aged ≥ 18 years and ≤ 80 years
• Written informed consent
• Adequate haematological, liver, renal function

Resectability

• Patients categorized as having resectable locally advanced cancer
• Favorable general condition

Exclusion Criteria:

Resectability

• Diagnosis of metastatic disease
• Clear indication of involvement of pelvic wall(s), on imaging.
• Peritoneal carcinomatosis, portal vein occlusion, ascites, non-regional lymph nodes
• Histology other than adenocarcinoma
• Obstructed rectal carcinoma without defunctionalizing colostomy

Prior treatment

• Previously undergone treatment for this disease
• Prior chemotherapy for colorectal cancer
• Prior chemotherapy for other malignancies in past 12 months
• Prior radiotherapy other than skin cancer
• Concomitant use of St John's Wort
• Treatment with any other investigational agent
• Current use of full-dose of warfarin for therapeutic

Other conditions

• Confirmed or suspected brain metastases
• History or evidence of CNS disease
• Past or current history of other malignancies
• Clinically significant cardiovascular disease
• Evidence of bleeding diathesis or coagulopathy
• Known hypersensitivity to any of the study drugs
• Serious, non-healing wound, ulcer or bone fracture
• Major surgical procedure or significant traumatic injury within 28 days prior to treatment
• Disease or condition that contraindicates the use of an investigational drug
• Life expectancy less than 5 years
• Inability or unwillingness to comply with the protocol
• Neuropathy ≥ Gr.2
• History of ulcerative colitis or Crohn's disease
• Pelvic abscess or perforated pelvic carcinoma

Pregnancy / Contraception

• Pregnancy or lactation
• Positive serum pregnancy test within 7 days of starting study treatment