The goal of this clinical research study is to learn if panitumumab can help to control advanced cancer of the small bowel or ampulla of Vater. The safety of this drug will also be studied.

Panitumumab is designed to "turn off" a protein that is important in cell growth. This may stop the growth of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive the study drug during 14 day study "cycles."

On Day 1 of every cycle, you will receive panitumumab by vein over about 60-90 minutes.

Study Visits:

On or before Day 1 of each cycle:

• You will have a physical exam, including measurement of your weight.
• Your performance status will be recorded.
• You will be asked about any symptoms you may be experiencing and any drugs you may be taking.
• Blood (about 2 tablespoons) will be drawn for routine tests.

Every 4 cycles:

• You will have a chest X-ray or a computed tomography (CT) scan of your chest to check the status of the disease.
• You will have a CT or MRI scan to check the status of the disease. If your scan shows that you are responding to the treatment, you will have another CT or MRI scan 6 weeks later.

Length of Study:

You may continue receiving the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

End-of-Treatment:

After you stop taking the study drugs for any reason, you will have an end-of-treatment visit. The following tests and procedures will be performed:

• You will have a physical exam, including measurement of your weight.
• Your performance status will be recorded.
• You will be asked about any symptoms you may be experiencing and any drugs you may be taking.
• Blood (about 2 tablespoons) will be drawn for routine tests.
• If the doctor thinks it is needed, you will have a CT or MRI scan of the abdomen and pelvis to check the status of the disease.

Follow-Up:

Thirty (30) days after your last dose of study drug(s), you will be asked about any symptoms you may be experiencing and any drugs you may be taking. If you are unable to come to MD Anderson for this, the study staff will call you and ask you these questions. This call will last about 30 minutes.

You will then be called every 3 months and asked the same questions. Each call will last about 15-30 minutes.

If you are taken off study treatment for reasons other than the disease getting worse, you will have a CT or MRI scan of the abdomen and pelvis to check the status of the disease every 12 weeks (+/- 2 weeks) after the End-of-Treatment visit. This will be done until the disease gets worse and if you do not start any other anti-cancer treatment.

This is an investigational study. Panitumumab is commercially available and FDA approved to treat a certain type of colorectal cancer. Its use in this type of cancer is investigational.

Up to 27 patients will take part in this study. All will be enrolled at MD Anderson.

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 progression on or intolerance to treatment with a fluoropyrimidine and oxaliplatin. Recurrence of disease within 6 months from the completion of adjuvant therapy with both a fluoropyrimidine and oxaliplatin is considered progression.
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 2 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 - 2.
8. Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,000/ul; b) Platelets =/>75,000/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 <2 x ULN.
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 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 may not be receiving any other investigational agents nor have received any investigational drug 30 days prior to enrollment.
3. 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.
4. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
5. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with panitumumab, breast feeding must be discontinued.
6. Age <18 years. Because no dosing or adverse event data are currently available on the use of panitumumab in patients <18 years of age, children are excluded from this study.

Adverse event collection from date of first treatment to 8 years