Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Study Overview
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Brief Summary
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Determine if genotype-directed neoadjuvant chemoradiation, using information from the thymidylate synthase promoter polymorphism, result in a greater degree of tumor downstaging in high risk patients compared to historical controls.

Official Title
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Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Conditions
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Rectal Carcinoma

Intervention / Treatment
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* Drug: 5FU
* Radiation: Radiation
* Procedure: Surgery of resectable lesions
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven adenocarcinoma of the rectum Lesion evaluated by surgeon and found to be resectable Stage T3 or T4 disease on radiography or ultrasound Karnofsky Performance Status at >60 Laboratory criteria: Absolute neutrophil count >= 1.5 K Platelets >= 100 K Total Bilirubin <= 2.0; SGOT and Alkaline Phosphatase <= 2 x upper limit of normal Creatinine < 2.0 Informed consent signed Patients with distant metastatic disease will be eligible if they satisfy all other conditions. Exclusion Criteria: Pregnant women, children < 18 years, or patients unable to give informed consent Patients with a past history of pelvic radiotherapy. Patients with prior malignancy in the past 5 years except: skin cancer or in-situ cervical cancer. However, patients with synchronous adenocarcinomas are eligible provided either (a) the synchronous adenocarcinoma was in a removed pedunculated polyp and did not invade the stalk or (b) the synchronous adenocarcinoma was in a removed polyp that lay within the surgical field (extent of resection would not be changed) or (c) the synchronous adenocarcinoma is smaller than the index rectal cancer and lies completely within the radiation field (clinically favorable second lesion and the extend of radiation and surgery would not be changed). Patients with known allergy to 5-fluorouracil or irinotecan

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)<br>Radiation 45 Gy in 25 fractions to the pelvis. 5FU CIVI 225 mg/m2/day by CIVI during radiation Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. | Drug: 5FU<br> <br> * Other names: 5-fluorouracil;Radiation: Radiation<br> <br> Procedure: Surgery of resectable lesions<br> <br> |
| Experimental: Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)<br>Radiation 45 Gy in 25 fractions to the pelvis. 5FU CIVI 225 mg/m2/day by CIVI during radiation Irinotecan 50 mg/m2 IV weekly for 5 doses. Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. | Drug: 5FU<br> <br> * Other names: 5-fluorouracil;Radiation: Radiation<br> <br> Procedure: Surgery of resectable lesions<br> <br> Drug: Irinotecan<br> <br> * Other names: Camptosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Tumor Downstaging Compared With Historical Controls. | Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%. | 1 year after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rates | Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0). Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0). pCR rate of historical controls is 8%-14%. | 1 year after enrollment | 
| Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation. | The questionnaire is encouraged but not required. | Prior to start of study treatment and 3-6 weeks post completion of radiation therapy | 
| Determine Patient Fears and Expectations of Pharmacogenetics. | The questionnaire is encouraged but not required. | Prior to start of study treatment and 3-6 weeks post completion of radiation therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal, rectum, cancer, carcinoma