Capecitabine and Radiation Therapy With or Without Panitumumab in Treating Patients With Advanced Rectal Cancer

OBJECTIVES:

• To assess the efficacy and safety of neoadjuvant capecitabine and concurrent 3-dimensional conformal radiotherapy with vs without panitumumab in patients with advanced K-ras unmutated rectal cancer.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, T stage (T3 vs T4), tumor localization measured from caudal part of the tumor to the anocutaneous line (< 10 cm vs ≥ 10 cm), and number of EGFR gene copies (< 2.9 vs ≥ 2.9). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive panitumumab IV over 30-90 minutes on days 1, 15, 29, 43, and 57 and oral capecitabine twice daily on days 8-40. Beginning on day 8, patients undergo daily fractions of 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning approximately 6 weeks after completion of panitumumab and chemoradiotherapy, patients undergo surgery.
• Arm II: Patients receive oral capecitabine twice daily on days 1-33. Patients undergo concurrent 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning 6 weeks after completion of chemoradiotherapy, patients undergo surgery.

After completion of study therapy, patients are followed periodically for up to 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced adenocarcinoma of the rectum with or without nodal involvement

• Stage mrT3-4 and/or mrN1-2, M0
• Tumors must express wild type K-ras gene
• No distant metastasis

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Able to undergo surgery
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 100 g/L
• Creatinine clearance ≥ 50 mL/min
• AST ≤ 2.5 times upper limit normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must agree to use effective contraception during and for 12 months after completion of study
• No malignancy within the past 5 years with the exception of adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
• No psychiatric disorder that would preclude understanding study-related information, giving informed consent, or complying with oral drug intake
• No prior existing conditions that would preclude radiotherapy
• No clinically significant (i.e., active) cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmia even if controlled with medication) or myocardial infarction within the past 12 months
• No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• No serious underlying medical condition that, in the judgement of the investigator, could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
• No known dihydropyrimidine dehydrogenase deficiency
• No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

• More than 30 days since prior treatment in a clinical trial
• No other concurrent experimental drugs, anticancer therapy, or investigational treatments
• No prior treatment for rectal cancer
• No prior anti-EGFR antibody therapy (e.g., cetuximab) or small-molecule EGFR inhibitors (e.g., erlotinib hydrochloride)
• No concurrent treatment with brivudine, lamivudine, ribavirin, or any other nucleoside analogues
• No organ allografts
• No concurrent drugs contraindicated for use with the trial drugs
• No other concurrent anti-EGFR-targeting agents
• No other concurrent radiotherapy