FOLFOX Chemotherapy Regimen (5-FU, Leucovorin, Oxaliplatin) in Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title: Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined With FOLFOX Chemotherapy in Metastatic Colorectal Cancer (CA180048)

Status Completed

Clinical Trial Summary

The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of a combination of dasatinib, cetuximab, and FOLFOX (5-fluorouracil [5-FU], leucovorin [LV], and Eloxatin [oxaliplatin]) that can be given to patients with metastatic colorectal cancer. The safety of these drugs in combination will also be studied.

The goal of the Phase II part of this clinical research study is to learn if dasatinib given in combination with FOLFOX with or without cetuximab can help to control metastatic colorectal cancer.

Clinical Trial Description

Cetuximab is a drug designed to block the activity of EGFR, a protein on the surface of some tumor cells that may cause the cells to grow. Blocking EGFR may stop or slow the growth of tumor cells. Dasatinib is a drug that inhibits a protein called c-Src. High levels of c-Src may make it harder for chemotherapy to work against the cancer. If dasatinib can inhibit c-Src, the chemotherapy may be more effective against the cancer. FOLFOX is a drug combination frequently used to treat colon or rectal cancer that has spread to other parts of the body. FOLFOX is designed to kill rapidly dividing cells by preventing DNA (the genetic material of cells) from duplicating.

Kirsten Rat Sarcoma (KRAS) Testing:

Recent studies have found that cetuximab, when given alone or in combination with other chemotherapy drugs, was not effective when given to patients with colorectal cancer that had a KRAS gene mutation.

If you take part in the Phase I part of this study, your tumor tissue from a previous biopsy or surgery will be used to test for KRAS mutation. If you have the KRAS gene mutation, you will not take part in this study.

If you take part in the Phase II part of this study, your tumor tissue from a previous biopsy or surgery will be used to test for KRAS mutation. If you have the KRAS gene mutation, you may take part in the study but you will not receive cetuximab.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group (Phase I or Phase II) based on when you join this study.

If you are enrolled in the Phase I portion, the dose of dasatinib you will receive will depend on when you joined the study. Three (3) to 6 participants will be entered at each dose level. Each new group of participants will receive a higher dose, until the highest tolerable dose is found. Once the highest tolerable dose is found, 12 participants will be enrolled at that dose level. Your doctor will tell you what dose level you will be receiving and how this dose compares to the doses other participants have received. The starting dose of cetuximab and FOLFOX will be the same for all participants. The dose of dasatinib will be increased with the next group of 3-6 participants. Every 14 days is considered 1 study "cycle".

If you are enrolled in the Phase II portion, you will receive the dose of dasatinib found to be best tolerated in the Phase I portion. You will also receive FOLFOX. If you do not have the KRAS gene mutation, you will also receive cetuximab. Every 14 days is considered 1 study "cycle".

Central Venous Catheter (CVC) Placement:

Before receiving the study drugs, you will have a CVC placed. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

Study Drug Administration:

You will take dasatinib by mouth once a day, every day during this study. Your study doctor and research nurse will tell you how many pills you will take. Dasatinib should be taken at the same time each day, with or without meals. If you miss a dose of dasatinib, you should not double the next dose. It is important to take dasatinib with water, and not fruit juices. You should not drink grapefruit juice or eat grapefruit while you are on this study. Dasatinib should not be touched by children, pregnant women, or women who are breastfeeding. If a caregiver must handle the drug, a protective glove should be worn.

While you are taking dasatinib, you will be given a drug diary. In this diary, you will write down the date, the time, and the number of dasatinib tablets taken. Certain drugs and herbal supplements may not be taken while you are receiving dasatinib. These drugs could affect how your body breaks down dasatinib, which could have a bad effect on you. Your doctor will give you a list of drugs and herbal supplements that you must not take while on this study. You must tell your doctor before taking any new drugs while on this study.

On Day 1 of every cycle, you will receive oxaliplatin and LV through the CVC over about 2 hours. On Day 1, you will receive 5-FU through a portable pump for the next 46 hours. If you are receiving cetuximab in the Phase I portion of the study, you will receive it on Days 1 and 8 through the CVC over about 2 hours. If you are receiving cetuximab in the Phase II portion of the study, you will receive it on Day 1 through the CVC over about 2 hours.

Study Visits for Phase I:

If you are enrolled at the highest tolerable dose level, you will have 2 core liver biopsies. The liver tissue will be studied to learn the effect of the study drugs on stopping the protein c-Src. You will have 2 liver biopsies collected. The first liver biopsy will be collected before you start the study drugs, and the second will be performed in either Cycle 2 or 3. Before the liver biopsy, you will receive fluids and drugs for relaxation and/or pain through an needle in your arm or hand. You will be awake during the biopsy. A radiologist will find the tumor in the liver with the help of radiographic imaging procedures such as an ultrasound or CT scan. Your skin around this area will be cleansed, and a local anesthetic will be given. A long, hollow needle will be inserted through the skin into the liver tumor, and a tissue sample(s) will be taken.

On Day 8, blood (about 1-2 tablespoons) will be drawn for routine tests.

You will have extra blood samples drawn (1 tablespoon each time) before receiving the study drugs and on Day 8 of Cycles 2 and 4. This blood will be drawn at the same time as your routine blood tests are drawn. These blood samples will be used to develop tests that may help doctors be able to predict who will best benefit from dasatinib.

If you are enrolled in the group that receives the highest tolerable dose level, the Day 8 blood draw during cycle 2 will not be performed. Instead, blood will be collected at the time of the liver biopsy that is to be performed between Days 8-14 of cycle 2 or 3 about 2 to 6 hours after taking the daily dose of dasatinib.

Study Visits for Phase II:

You will have extra blood samples drawn (1 tablespoon each time) before receiving the study drugs and at the end of every 4 cycles. This blood will be drawn at the same time as your routine blood tests are drawn. These blood samples will be used to develop tests that may help doctors be able to predict who will best benefit from dasatinib.

Before the start of each new cycle and when you stop study treatment, you will be asked to complete a questionnaire about any symptoms you may be experiencing. The questionnaire will take up to 5 minutes to complete.

Once you stop receiving study drugs, the study team will contact you by telephone every 3 months to check how you are doing. Each phone call will take about 5 minutes.

Phase I and Phase II:

Before each new cycle, you will be asked questions about any side effects you may have had. At each visit, it is important to tell the study staff about any drugs you are currently taking. You will have a physical exam, including measurement of your vital signs and weight. You will have a performance status evaluation. Blood (about 1-2 tablespoons) will be drawn for routine tests.

Women who are able to become pregnant will have a blood or urine pregnancy test every month.

If you experience severe side effects, the study drugs may be delayed, stopped, or you may receive smaller doses of the drugs.

You may remain on this study for as long as you are benefiting. You will be taken off this study if the disease gets worse or intolerable side effects occur.

Once you are off-study, you will have an end-of-study visit. At this visit, blood (about 3 tablespoons) will be collected for routine tests. You will be asked questions about any side effects you may have had and about any drugs you are currently taking. You will have a physical exam, including measurement of your vital signs and weight. You will have a performance status evaluation. If not performed recently, you will have a CT scan or MRI scan of your chest, abdomen and pelvis to check the status of the disease. If you are having side effects after you stop receiving the study drugs, you will be contacted by phone to check how you are feeling, or you will have follow-up visits until the side effects have gone away.

This is an investigational study. Dasatinib is FDA approved for the treatment of leukemia. Its use in this study, for this disease, is considered to be investigational. Cetuximab, 5-FU, LV, and oxaliplatin are all FDA approved and commercially available for the treatment of colorectal cancer. Up to 83 patients will take part in this study. All patients will be enrolled at MD Anderson. ;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

• NCT number: NCT00501410
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: April 23, 2007
• Completion date: March 3, 2017