Preoperative Chemoradiotherapy With Cetuximab in Rectal Cancer

A Phase II Study of Pre-Operative Concurrent Chemoradiotherapy With Cetuximab, Irinotecan, and Capecitabine in Resectable Rectal Cancer

This study is to estimate the pathologic complete response rate of cetuximab, irinotecan, and capecitabine concurrent with radiotherapy given preoperatively in patients with resectable rectal cancer.

Daily fractions of radiotherapy at 1.8 Gy to total of 45 Gy to tumor and draining lymph nodes and followed by a coned-down boost of 5.4 Gy to the tumor are delivered concurrently with chemotherapy.

Cetuximab 400 mg/m2 is given intravenously on D-6 (1 week before radiation), followed by 250 mg/m2 once a week (D 1, 8, 15, 22 & 29).

Administration of irinotecan and capecitabine starts on day 1 of radiotherapy. Capecitabine is administered orally at a dose of 825 mg/m2 twice daily during weekdays (Monday to Friday) during radiotherapy. Irinotecan 40 mg/m2 is given intravenously once a week (D 1, 8, 15, 22 & 29).

Four to eight weeks after completion of chemoradiotherapy, curative surgery is performed.

Safety evaluation of the study will be performed after the first 6 patients treated. If more than 1 out of 6 patients received less than 70-80% of planned dose of capecitabine or irinotecan, the dosage of chemotherapy in the further study patients will be adjusted by a protocol amendment.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the rectum
• Distal margin of tumor located from 0 to 8 cm from anal verge
• Stage T3/T4 ± N+ by MRI ± endorectal ultrasonography
• ECOG performance status 0-2
• No prior chemotherapy, radiotherapy to pelvis, immunotherapy, and EGFR pathway targeting therapy
• Adequate organ functions
• Patients must sign the informed consent

Exclusion Criteria:

• Malignant disease of the rectum other than adenocarcinoma or arisen from chronic inflammatory bowel disease
• Any defined hereditary colorectal cancer
• Any unresected synchronous colon cancer
• R0 resection of tumor is not clinically possible
• Any distant metastasis
• Intestinal obstruction or impending obstruction, but decompressing colostomy is permitted
• Any previous or concurrent malignancy other than non-melanoma skin cancer or in situ cancer of uterine cervix
• Any other morbidity or situation with contraindication for chemoradiotherapy
• Patients with history of significant gastric or small bowel resection, or malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of capecitabine
• History of severe pulmonary disease
• Pregnant or lactating women or patients of childbearing potential not predicting adequate contraception