IRB Number:

06-006631

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

Adenocarcinoma of the small bowel is a rare form of cancer. At this time, there is no standard treatment known to make it better. A small study was done and that study showed that combining the drugs irinotecan, oxaliplatin, 5-fluorouracil, and leucovorin made tumors get smaller in some patients whose cancer had spread to other parts of their body. In another study, though, this treatment caused some bad side effects. This new study has included a change of the 5-fluorouracil and leucovorin to a similar oral medication called capecitabine. It also tests one of the patient's genes to determine the dose of chemotherapy to be used. The investigators made these changes to try to make the drug combination safer for use in patients.
The main purpose of this research study is to see if small bowel cancer tumors get smaller when treated with irinotecan, oxaliplatin, and capecitabine (a newer, oral form of 5-fluorouracil) based on the dose of the medications determined by a gene called UGT1A1. The researchers will also look at what the side effects of the chemotherapy drugs are.


The gene UGT1A1 makes a protein that affects how the chemotherapy drugs, especially the irinotecan, affect a patient's body. People with certain type of the UGT1A1 are more likely to get the side effects from one of the drugs, irinotecan. In this research study, the researchers will test a sample of the patient's blood to find out what type of UGT1A1 they have and that will help the researchers decide what dose of the chemotherapy drugs to give the patient. People with different UGT1A1 types will get different doses of this chemotherapy.

Part of the purpose of this research study is to try two different ways to help patients have fewer side effects when irinotecan, oxaliplatin, and capecitabine are used together.
- The researchers will look to see if giving different doses of this chemotherapy to patients with different UGT1A1 types will cause fewer side effects. The dose may affect how bad the side effects are.
- The researchers will use the newer version of 5-fluorouracil called capecitabine. Capecitabine is a tablet that will be taken by mouth instead being injected into a vein.
Also, the research staff want to find out if this chemotherapy works better in some types of small bowel tumors than others. Tumor types may be different, for example, because of where in the small intestine the tumor started or because of errors in the DNA. The researchers will look to see if patients with small bowel cancer also have another disease called celiac disease (also called sprue) and how that affects treatment. The research staff will look at patients blood samples and tissue samples to find out what type of small bowel tumor the patient has and whether or not they also have celiac disease.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with adenocarcinoma of the small intestine which is not able to be removed surgically or has spread to other parts of the body
-At least two weeks since any radiation treatment
-At least four weeks since any prior surgery

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

If patients agree to be in the study, they will be asked to participate in the following:

Before the study
Before taking part in this study, patients will have blood drawn. Some of this blood will be used to find out what type of UGT1A1 gene the patient has and some will be used later on in the study. In this study, the researchers will only look at three types of the UGT1A1 gene. Most people will have one of those three types, but a few patients may have a different type. If patients have one of the three UGT1A1 gene types that is being studied, they can be enrolled in the study. If not, a patient will not be able to be part of this study.

The results of the blood test will also be used to decide what dose of chemotherapy the patient will get in the study. It may take up to one week before the patient and the research doctor learn the test results and the patient can start treatment on the study.

Patients will need to have the following exams, tests or procedures to find out if they can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if the patient does not join the study. If the patient has had some of them recently, they may not need to be repeated. This will be up to the study doctor.

-Medical history and physical exam, including height/weight and rating of how well the patient performs activities of daily living
- Pregnancy test if a woman able to become pregnant
- Tumor measurement
- Chest X-ray or CT scan (a picture of body's organs)
- Routine blood tests will be done along with other blood tests to check for signs of disease activity and complications, and to compare to blood samples taken after
the patient's treatment.
- Samples of the patient's tumor tissue which have already been taken will also be submitted so that their diagnosis of small bowel cancer can be confirmed. The researchers may ask for tumor samples from the hospital that took the original sample. If so, patients will need to sign a release form to allow the hospital to give the researchers the sample.

During the study:
Part of the blood sample that was taken before the patient was registered on this study will now be tested to see if they have a disease of the intestine called celiac disease. Celiac disease is sometimes seen in people who have small bowel cancer. If patients do have celiac disease, it may affect what side effects they get from the chemotherapy. If the test for celiac disease is positive, the patient and their physician will be notified and some specific dietary
recommendations may be made.

During the study, patients will need the following tests and procedures.
-Medical history, physical exam, including weight and a rating of how well patient performs activities of daily living will be done before each chemotherapy treatment.
- Routine blood tests will be done before each chemotherapy treatment and weekly in between treatments
- Tumor measurements will be done every two cycles (every six weeks.).
- Chest x-ray about every three months unless a CT scan is being done to measure the patient's tumor every six weeks. If the CT scan is being done, the chest X-ray will not be needed.

When starting chemotherapy, patients will be given irinotecan, oxaliplatin, capecitabine every three weeks. One cycle is 3 weeks. Patients will get chemotherapy until they have a complete response, their tumor gets worse, or the patient or their doctor decides that the side
effects are too bad.

When you are finished taking the chemotherapy:
If the patient's cancer goes into remission (completely disappears on imaging studies) for two evaluations in a row while on treatment, the patient and their physician will have the option of stopping treatment.

If the disease gets worse, patients will continue to get treatment for 12 cycles (nine months).
After 12 cycles or if the side effects are too bad or if the patient or their doctor decide they should not get any more treatment, they can stop chemotherapy.
If patients decide to stop treatment and then their tumor starts to get worse, they can start treatment again without going back on the study.

How long will the Study run?

Patients will be in the study for at least nine months (12 cycles) unless their cancer completely disappears or the side effects are too bad. Then they will need to
return to the clinic for study visits every six weeks for two years after treatment is stopped. The research staff will also contact the patient for follow-up information for the rest of their life.

Sponsor(s): North Central Cancer Treatment Group (NCCTG)

Study Activation/Registration Date: 06/29/2007

IRB Review and Approval Date: 06/07/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 33 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Robert R. McWilliams, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/14/2008