Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00501410
Status:
COMPLETED
Last Update Posted:
2019-08-28
First Post:
2007-07-12
Brief Title:
FOLFOX Chemotherapy Regimen 5-FU Leucovorin Oxaliplatin in Metastatic Colorectal Cancer
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined With FOLFOX Chemotherapy in Metastatic Colorectal Cancer CA180048
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed 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 andor 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 samples 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
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 andor 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 samples 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2015-01568 | REGISTRY | NCI CTRP | None |