Neoadjuvant Celecoxib and Capecitabine Combined With Pelvic Irradiation in Treating Patients With Stage II or Stage III Adenocarcinoma (Cancer) of the Rectum

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Celecoxib may also make tumor cells more sensitive to chemotherapy and radiation therapy. Giving celecoxib with capecitabine and radiation therapy before surgery may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is studying how well giving neoadjuvant celecoxib together with capecitabine and pelvic irradiation works in treating patients with stage II or stage III adenocarcinoma (cancer) of the rectum.

Detailed Description
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OBJECTIVES: Primary Determine the pathological complete response rate in patients with stage II or III adenocarcinoma of the rectum treated with neoadjuvant celecoxib and capecitabine in combination with pelvic irradiation. Secondary Determine the safety and tolerability of this regimen in these patients. Determine the rectal function of patients treated with this regimen. Determine the time to recurrence or progression and survival time of patients treated with this regimen. Correlate cellular and molecular markers in pretreatment tumor samples with response in patients treated with this regimen. OUTLINE: This is a multicenter study. Neoadjuvant chemoradiotherapy: Patients receive oral celecoxib twice daily on days 1-7 and oral capecitabine twice daily on days 1-5. Patients undergo pelvic radiotherapy once daily on days 1-5. Courses repeat weekly for 5.5 weeks. Surgery: Patients undergo surgery 4-6 weeks after completion of neoadjuvant chemoradiotherapy. Adjuvant chemotherapy: Patients with a curative resection receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for up to 4 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Official Title
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A Phase II Trial Of Celecoxib (Celebrex) And Capecitabine (Xeloda) Combined With Pelvic Irradiation As Neoadjuvant Treatment Of Stage II or III Adenocarcinoma Of The Rectum

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: celecoxib
* Radiation: radiation therapy
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed rectal adenocarcinoma Clinical stage T3, N0, M0 OR any T, N1-3, M0 disease Treatment with neoadjuvant chemotherapy and pelvic radiotherapy is indicated All disease must be encompassable within standard pelvic radiotherapy fields Distal border of the tumor must be at or below* the peritoneal reflection, defined as within 12 cm of the anal verge by endoscopy NOTE: *If a portion of the tumor is below the peritoneal reflection at the time of surgery, patients are eligible regardless of the distance of the tumor determined at endoscopy Tumor must be determined to be clinically resectable Tumor may not be clinically fixed Negative margins by routine examination of an unanesthetized patient Transmural penetration of tumor through the muscularis propria by CT scan, endorectal ultrasound, or MRI No distant metastatic disease No evidence of tumor outside the pelvis, including any of the following: Metastatic inguinal lymphadenopathy Peritoneal seeding Liver metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ upper limit of normal (ULN) AST ≤ 3 times ULN Alkaline phosphatase ≤ 4 times ULN if AST < ULN Renal Creatinine clearance ≥ 30 mL/min No renal impairment Cardiovascular No congestive heart failure No symptomatic coronary artery disease No uncontrolled cardiac arrhythmias No myocardial infarction No history of transient ischemic attacks or stroke No other clinically significant cardiac disease Gastrointestinal No bleeding peptic ulcer disease within the past 12 months No lack of physical integrity of the upper gastrointestinal tract No malabsorption syndrome No active inflammatory bowel disease Must be able to swallow study drugs Other No dihydropyrimidine dehydrogenase deficiency No history of uncontrolled seizures No CNS disorders No clinically significant psychiatric illness that would preclude study compliance or giving informed consent No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No known sensitivity to NSAIDs, sulfonamides, or aspirin No other serious medical illness that would preclude study treatment No other conditions that would preclude study participation Must be able to tolerate major surgery that may include abdominal-perineal resection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior systemic anticancer chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior radiotherapy to the pelvis Surgery See Disease Characteristics More than 3 weeks since prior major surgery and recovered Other At least 7 days since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin No other concurrent investigational drugs No other concurrent anticancer treatment No concurrent NSAIDs No concurrent primary prophylactic therapy for hand-foot syndrome No concurrent loperamide prophylaxis for diarrhea No concurrent sorivudine or brivudine

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: celecoxib + capecitabine + radiation + surgery<br>Neoadjuvant chemoradiotherapy: Patients receive oral celecoxib twice daily on days 1-7 and oral capecitabine twice daily on days 1-5. Patients undergo pelvic radiotherapy once daily on days 1-5. Courses repeat weekly for 5.5 weeks. Surgery: Patients undergo surgery 4-6 weeks after completion of neoadjuvant chemoradiotherapy. Adjuvant chemotherapy: Patients with a curative resection receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for up to 4 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. | Drug: capecitabine<br> <br> Drug: celecoxib<br> <br> Radiation: radiation therapy<br> <br> Procedure: surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of successes |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time |  | Up to 5 years | 
| Time-to event analyses |  | Up to 5 years | 
| Time to disease progression/recurrence |  | Up to 5 years | 
| Time to recurrence |  | Up to 5 years | 
| Time to first progression |  | Up to 5 years | 
| Survival |  | Up to 5 years | 
| Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire |  | Up to 5 years | 

 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