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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the rectum stage II rectal cancer stage III rectal cancer	Drug: capecitabine  Drug: celecoxib  Procedure: adjuvant therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase II

Further Study Details: 

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.

PROJECTED ACCRUAL: A total of 23-55 patients will be accrued for this study within 10-28 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Coborn Cancer Center, Saint Cloud,  Minnesota,  56303,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States; Recruiting
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada; Recruiting

Study chairs or principal investigators

Frank Sinicrope, MD,  Study Chair,  Mayo Clinic Cancer Center   
James A. Martenson, MD,  Mayo Clinic Cancer Center   
Richard L. Deming, MD,  Therapeutic Radiology Associates, P.C.   
Heidi Nelson, MD,  Mayo Clinic Cancer Center   
James Dewitt Bearden, MD,  CCOP - Upstate Carolina   

Study ID Numbers:  CDR0000360666; NCCTG-N0346; NCT00081224
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00081224
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08