Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed colorectal adenocarcinoma

- Metastatic disease

- Wild type KRAS (no mutation) by allelic discrimination on tumor DNA

- Measurable disease (≥ 10 mm) per modified RECIST criteria

- Previously treated for metastatic disease with oxaliplatin and fluorpyrimidines
(i.e., fluorouracil/folinic acid or capecitabine) with or without bevacizumab, and
irinotecan hydrochloride alone or in combination with fluorpyrimidines (i.e.,
fluorouracil/folinic acid or capecitabine) with or without bevacizumab

- Must have paraffin-embedded tissue or unstained tumor slides from primary or
metastatic tumor available for correlative studies

- Must be registered with a national health care system (CMU included)

- No CNS metastases unless previously treated or asymptomatic, provided patient has
been off steroids for at least 30 days prior to study treatment

PATIENT CHARACTERISTICS:

- WHO performance status of 0-2

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Creatinine < 150 μmol/L or creatinine clearance > 30 mL/min

- AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

- ALT ≤ 3 times ULN (5 times ULN if liver metastases present)

- Bilirubin ≤ 1.5 times ULN

- Magnesium normal

- No significant cardiovascular disease, including unstable angina or myocardial
infarction within the past 6 months

- No history of treated or untreated ventricular arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double barrier contraception during and for 6
months after completion of study treatment

- No other malignant tumors within the past five years except basocellular carcinoma,
in situ cancer of the cervix or uterus, or any UDAW cancers for which there has been
complete resection for at least three years

- No known hypersensitivity to an excipient (vehicle) of panitumumab or known
hypersensitivity of irinotecan trihydrate chlorhydrate or known hypersensitivity
excipient (vehicle) of irinotecan hydrochloride

- No history of interstitial pneumonitis, pulmonary fibrosis or evidence of
interstitial pneumonitis, or pulmonary fibrosis on baseline chest CT scan

- No active inflammatory bowel disease, other bowel disease causing chronic diarrhea
(defined as > 4 loose stools per day), or bowel occlusion

- No history of Gilbert syndrome

- No history of any medical condition that may increase the risks associated with study
participation or may interfere with the interpretation of the study results

- No known positive test for HIV infection, hepatitis C virus, chronic active hepatitis
B infection

- No comorbid disease that would increase risk of toxicity

- No disorder that would compromise the patient's ability to give written informed
consent and/or comply with study procedures

- Must be willing and able to comply with study requirements

- No grade IV toxicity associated with a past treatment with irinotecan hydrochloride

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 14 days since prior treatment for systemic infection

- No prior or concurrent anti-EGFR antibody therapy (e.g., cetuximab) or treatment with
small molecule EGFR tyrosine kinase inhibitors (e.g., erlotinib hydrochloride)

- Patients who discontinued their first dose of anti-EGFR therapy (i.e.,
cetuximab) because of an infusion reaction are eligible

- More than 30 days since prior and no other concurrent investigational agent (no delay
for non-investigational treatment)

- More than 14 days since prior CYP3A4 enzyme, including anticonvulsant medication
(e.g., phenytoin, phenobarbital, or carbamazepine)

- More than 14 days since prior rifampicin

- More than 14 days since prior radiotherapy and recovered

- More than 7 days since prior and no concurrent ketoconazole

- More than 28 days since prior and no concurrent major surgical procedure

- Concurrent topical, oral, or IV antibiotics used to treat skin- or nail-related
toxicities are allowed at the investigator's discretion

- No other concurrent experimental or approved anti-tumor therapies (e.g.,
bevacizumab), chemotherapy other than irinotecan hydrochloride, non-palliative
radiotherapy, or systemic steroids (except when used for symptomatic skin- or
nail-related toxicities requiring withholding of the panitumumab dose, as
chemotherapy premedication, or for an infusion reaction)

- No concurrent millepertuis (i.e., Hypericum perforatum)

- No concurrent phenobarbital, clarithromycin, erythromycin, HIV protease inhibitors,
cyclosporine or tacrolimus, or nefazodone

- Concurrent minor surgery, procedures, or surgery arising as needed or necessary
allowed

- Concurrent elective surgery allowed in patients eligible for surgical resection of
metastases as curative therapy