Capecitabine, Oxaliplatin, Selenomethionine, and Radiation Therapy in Treating Patients Undergoing Surgery For Newly Diagnosed Stage II or III Rectal Adenocarcinoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenomethionine may slow the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together With selenomethionine and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well selenomethionine works when given together with capecitabine, oxaliplatin, and radiation therapy in treating patients undergoing surgery for newly diagnosed stage II or stage III rectal cancer.

Detailed Description
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OBJECTIVES: Primary To determine the complete pathological response rate of the combination of capecitabine, oxaliplatin, selenomethionine, and radiotherapy in patients with stage II or III rectal adenocarcinoma. To determine the T-downstaging rate with this regimen in patients with stage II or III rectal adenocarcinoma. Secondary To determine the safety of this regimen by assessing toxicity and dose intensity of the various components of this regimen. To determine the rate of local relapse. To determine the rate of distant relapse. OUTLINE: Patients receive neoadjuvant therapy comprising oral selenomethionine twice daily for 1 week prior to radiotherapy and then once daily for 6 weeks. Patients also receive oxaliplatin IV over 2 hours on days 1-7 and oral capecitabine twice daily on days 1-5 for 6 weeks and undergo radiotherapy 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks after completion of neoadjuvant therapy, patients undergo curative-intent surgery. Beginning 4-8 weeks after surgery, patients may receive up to 9 courses of standard adjuvant combination chemotherapy (FOLFOX). Blood samples are collected at baseline and weekly during treatment and analyzed by absorption spectrophotometry for selenium measurement of drug concentration. Pharmacokinetic studies are also performed. After completion of study treatment, patients are followed for up to 5 years.

Official Title
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A Phase II Study of Capecitabine, Oxaliplatin and Selenomethionine and Radiation Therapy in Patients With Stage II and III Rectal Adenocarcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: selenomethionine
* Drug: capecitabine
* Drug: oxaliplatin
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: adjuvant therapy
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed rectal adenocarcinoma that is involving the distal 12 cm of the rectum (above the anal verge) Staged within 8 weeks prior to initiation of study by endoscopic ultrasound OR MRI or CT scan if endorectal ultrasound is non-conclusive or non-tolerable T3-T4 tumor or evidence of lymph node involvement defined by the presence of at least 1 enlarged peri-rectal lymph node No evidence of distant or known metastases PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100% Life expectancy > 1 year Leukocytes ≥ 3,000/µL Absolute neutrophil count ≥ 1,500/µL Platelet count ≥ 100,000/µL Total bilirubin ≤ upper limit of normal (ULN) AST/ALT ≤ 2.5 times ULN Creatinine ≤ ULN OR creatinine clearance ≥ 60 mL/min Able to receive oral medication Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other concurrent or previous malignancies unless disease free for > 5 years (excluding nonmelanoma skin cancer) No neuropathy ≥ grade 2 No history of allergic reaction attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or selenomethionine No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness/social situations that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: No prior radiotherapy to the pelvis No prior chemotherapy No other concurrent investigational or anticancer agents or therapies No concurrent vitamin B6 supplementation (except as part of a standard, multivitamin supplement)

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine, Oxaliplatin, Selenomethionine, Radiation Therapy<br>Oxaliplatin: 50 mg/m2 weekly x 5 Capecitabine 725 mg/m2BID on days of RT Selenomethionine: 4000mcg/m2 PO BID X 7 days prior to RT, then 4000mcg/m2 PO QD from first to last day of RT, including weekends | Dietary Supplement: selenomethionine<br> <br> Drug: capecitabine<br> <br> Drug: oxaliplatin<br> <br> Other: laboratory biomarker analysis<br> <br> Other: pharmacological study<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: therapeutic conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Pathological Response Rate |  | After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically. | 
| Rate of T-downstaging With Capecitabine, Oxaliplatin, Selenomethionine, and Radiotherapy |  | After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability as Assessed by NCI CTCAE Version 3.0 | Number of participants with any adverse event as assessed by NCI CTCAE version 3.0. | Adverse events were queried for and collected every cycle for the duration of treatment. | 
| Dose Intensity |  | During treatment with capecitabine, oxaliplatin, selenomethionine. | 
| Local Relapse Rate |  | For up to 5 years following surgery. | 
| Distant Relapse Rate |  | For up to 5 years following surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the rectum, stage II rectal cancer, stage III rectal cancer