Preoperative Chemoradiotherapy With Cetuximab in Rectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rectal Neoplasms, Neoadjuvant Treatment

Intervention / Treatment
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* Drug: Cetuximab, Irinotecan, Capecitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cetuximab, Irinotecan, Capecitabine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic stage Tumor regression grade |  | After operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity measured by NCICTC v3 |  | During chemoradiation | 
| Disease-free survival |  | Three year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cetuximab, Rectal neoplasms, Neoadjuvant treatment, Irinotecan, Capecitabine, Radiotherapy, Combination chemotherapy