A Phase II Study to Evaluate the Efficacy and Safety of Neoadjuvant Radiation in Combination With Capecitabine & Paniumumab With and Without Irinotecan in Patients With Localized Rectal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the distal rectum (0-9 cm
from the dentate line or 3-12 cm from the anal verge)

- T3 or T4 tumor or nodal involvement by endorectal ultrasound or CT scan or MRI

- Patients with any T status where tumor is close to but not involving the
sphincter who otherwise would be candidates for abdominoperineal resection are
eligible

- No known homozygotes to UGT1A1* 28

- No distant metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 3 times ULN

- Serum creatinine ≤ 1.5 times ULN

- Creatinine clearance ≥ 50 mL/min

- Magnesium normal

- Able to tolerate major surgery

- Able and willing to comply with study requirements

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 weeks (males) or
24 weeks (females) after completion of study therapy

- No prior diagnosis of interstitial lung disease

- No prior unanticipated severe reaction to fluoropyrimidine therapy or known
hypersensitivity to fluorouracil

- No other prior or concurrent invasive malignancy unless disease-free for ≥ 5 years

- No lack of physical integrity of the upper gastrointestinal tract, inability to
swallow tablets, or malabsorption syndrome

- No concurrent serious infections

- No clinically significant cardiovascular disease within the past year, including any
of the following:

- Myocardial infarction

- Unstable angina

- Symptomatic congestive heart failure

- Symptomatic coronary artery disease

- Serious uncontrolled cardiac arrhythmia

- No history of any medical or psychiatric condition or laboratory abnormality that, in
the opinion of the investigator, may increase risks associated with study
participation or investigational product(s) administration or may interfere with the
interpretation of the study results

- No known positivity for HIV, hepatitis C, or acute or chronic active hepatitis B

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy for rectal cancer

- No prior anti-EGFr antibody therapy (e.g., cetuximab)

- No prior treatment with small molecule EGFr inhibitors (e.g., gefitinib, erlotinib
hydrochloride, or lapatinib ditosylate)

- No prior therapeutic radiotherapy to the pelvis

- More than 28 days since prior major surgery

- More than 14 days since prior minor surgery

- At least 30 days since prior investigational agent or therapy

- At least 4 weeks since prior and no concurrent sorivudine or brivudine

- No concurrent chronic immunosuppressive agents (e.g., methotrexate or cyclosporine)

- No concurrent cimetidine