Inclusion Criteria:

1. Patients must have histologically confirmed adenocarcinoma of the small bowel or
ampulla of Vater that is either unresectable or metastatic.

2. Adequate tumor tissue available for KRAS mutational analysis or known KRAS wild-type
status.

3. Prior adjuvant chemotherapy for the treatment of adenocarcinoma of the small bowel or
ampulla of Vater is allowed. If prior adjuvant therapy was a fluoropyrimidine (5-FU
or capecitabine) or platinum agent, then last dose must have been administered =/> 26
weeks prior to first dose of study treatment with the exception that capecitabine or
5-FU administered as a radiosensitizing agent concurrently with external beam
radiotherapy at any time prior to study enrollment is allowed.

4. Patients must have measurable disease as per the revised Response Evaluation Criteria
In Solid Tumors (RECIST) criteria (Version 1.1).

5. If radiation was previously received, the measurable disease must be outside the
previous radiation field, unless this area has demonstrated evidence of radiographic
growth.

6. A minimum of 4 weeks must have elapsed from completion of any prior chemotherapy or
radiotherapy or surgery and the start date of study therapy.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

8. Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,500/ul; b)
Platelets =/>100,000/ul; c) Total bilirubin =/< 1.5 x ULN; in patients with known
Gilbert's syndrome direct bilirubin =/<1.5 x ULN will be used as organ function
criteria, instead of total bilirubin; d) AST (SGOT)/ALT (SGPT) < 3 x ULN; e)
Creatinine CrCl > 50 cc/min (Calculated creatinine clearance (CrCl) calculated using
the Cockcroft and Gault formula)

9. Negative urine or serum pregnancy test in women with childbearing potential (defined
as not post-menopausal for 12 months or no previous surgical sterilization), within
one week prior to initiation of treatment.

10. The effects of the combination of CAPOX and panitumumab on the developing fetus are
unknown. For this reason, women of childbearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control) prior to study
entry, for the duration of study participation, and for six months following the
completion of therapy. Should a woman become pregnant while participating in this
study, she should inform her treating physician immediately.

11. Patients must sign an Informed Consent and Authorization indicating that they are
aware of the investigational nature of this study and the known risks involved.

12. Magnesium level =/> lower limit of normal.

Exclusion Criteria:

1. Prior anti-epidermal growth factor receptor antibody therapy (eg. panitumumab or
cetuximab) or prior small molecule anti-epidermal growth factor receptor therapy (eg.
erlotinib) for adenocarcinoma of the small bowel or ampulla of Vater.

2. Patients who have received prior chemotherapy for metastatic disease are excluded.
Chemotherapy if given as a radiation-sensitizer is allowed.

3. Patients may not be receiving any other investigational agents nor have received any
investigational drug 30 days prior to enrollment.

4. Patients receiving therapeutic anticoagulation, such as Coumadin or low-molecular
weight heparin, for a venous thromboembolism are excluded. Anticoagulation for
reasons other than VTE (atrial fibrillation) is not a cause for exclusion, provided
that patients on Coumadin can be switched to low molecular weight heparin for the
duration of the study. The dose of low molecular weight heparin used will not be a
cause for exclusion.

5. Known history of dihydropyrimidine (DPD) deficiency.

6. Peripheral neuropathy of grade 2 or greater by Common Toxicity Criteria (CTCAE) 4.0.

7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit adherence with
study requirements.

8. Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation.

9. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung.

10. Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with oxaliplatin or capecitabine or panitumumab,
breast feeding must be discontinued.

11. Because of the interaction between coumadin and capecitabine patients taking
therapeutic doses of coumarin-derivative anticoagulants, are not eligible. Low-dose
Coumadin (e.g. 1 mg PO per day) in patients with in-dwelling venous access devices is
allowed but increased frequency of INR monitoring is recommended.

12. Age <18 years. Because no dosing or adverse event data are currently available on the
use of CAPOX and panitumumab in patients <18 years of age, children are excluded from
this study.