RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Intensity-modulated radiation therapy (radiation directed at the tumor more precisely than in standard radiation therapy) with incorporated boost (an increase in the amount of radiation given during treatment) may cause less damage to normal tissue. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy together with chemotherapy before surgery may shrink the tumor so it can be removed.

PURPOSE: This phase I trial is studying the side effects and best dose of neoadjuvant intensity-modulated radiation therapy with incorporated boost when given together with capecitabine in treating patients with locally advanced rectal cancer.

Condition	Treatment or Intervention	Phase
stage II rectal cancer stage III rectal cancer adenocarcinoma of the rectum	Drug: capecitabine  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: surgery	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated radiotherapy when combined with capecitabine before surgery in patients with locally advanced rectal cancer.

Secondary

• Determine the pathologic tumor response in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of boost intensity-modulated radiotherapy (IMRT).

Patients undergo neoadjuvant IMRT with incorporated boost once daily 5 days a week for 5 weeks. Beginning on the first day of radiotherapy, patients receive oral capecitabine twice daily 7 days a week for 5 weeks. Patients undergo surgical resection 4-8 weeks after completion of chemoradiotherapy.

Cohorts of 3-6 patients undergo escalating doses of boost IMRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline, at week 5 of chemoradiotherapy, before surgery, and then at 1, 3, and 12 months after surgery.

Patients are followed at 1, 3, and 12 months after surgery.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the rectum
• Distal border of the tumor within 12 cm of the anal verge by proctoscopic exam
• Clinical stage T3-4, N1-2 (stage II or III) disease by 2 of the following tests:
• Physical exam
• Transrectal ultrasound
• Pelvic CT scan
• Pelvic MRI
• No clinical evidence of metastatic disease

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No known, uncontrolled coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times normal
• Creatinine clearance > 50 mL/min

Cardiovascular

• No clinically significant cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No poorly controlled cardiac arrhythmias
• No myocardial infarction within the past year

Gastrointestinal

• No active inflammatory bowel disease
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome

Other

• No other prior or concurrent malignancy except inactive, non-invasive carcinoma of the cervix or non-melanoma skin cancer
• No concurrent serious, uncontrolled infection(s)
• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No known sensitivity to fluorouracil
• No prior uncontrolled seizures
• No CNS disorders that would preclude study participation
• No other medical or psychiatric condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for rectal cancer

Chemotherapy

• No prior chemotherapy for rectal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for rectal cancer
• No prior pelvic radiotherapy

Surgery

• More than 4 weeks since prior major surgery and recovered
• No prior surgery for rectal cancer

Other

• More than 4 weeks since prior participation in another investigational drug study
• No concurrent celecoxib

Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting

Study chairs or principal investigators

Gary Freedman, MD,  Principal Investigator,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000365462; FCCC-03606; NCT00084591
Record last reviewed:  May 2004
Last Updated:  April 5, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084591
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08