Phase I/II Study of Azacitidine and CAPOX (Capecitabine + Oxaliplatin) in Metastatic Colorectal Cancer Patients Enriched for Hypermethylation of CpG Promoter Islands
The Study Drugs:
Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the
function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting
genes may be able to work better.
Capecitabine is designed to interfere with the growth of cancer cells.
Oxaliplatin is designed to keep new cancer cells from growing.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 4 groups of up to 3-6 participants will be
enrolled in the Phase I portion of the study, and up to 30 participants will be enrolled in
Phase II.
If you are enrolled in the Phase I portion, the dose of azacitidine and oxaliplatin you
receive will depend on when you joined this study. All participants will receive the same
dose of capecitabine. The first group of participants will receive a low dose level of the
combination. Each new group will receive a higher dose of the combination than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of the combination of azacitidine, oxaliplatin, and capecitabine is found.
If you are enrolled in the Phase II portion, you will receive the combination of
azacitidine, oxaliplatin, and capecitabine at the highest dose that was tolerated in the
Phase I portion.
Central Venous Catheter (CVC):
Before you can begin to receive oxaliplatin on this study, you will have a CVC placed if you
do not have one already. 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:
A cycle of treatment is defined as 21 days.
Azacitidine will be injected under your skin on Days 1-5 of each cycle.
You will receive oxaliplatin by vein over 2 hours on Day 2 of each cycle.
You will take capecitabine by mouth 2 times each day on Days 1-14 of each cycle.
Capecitabine tablets should be taken 12 hours apart, within 30 minutes after eating a meal.
Study Visits:
Up to 3 days before or on Day 1 of each cycle, the following tests and procedures will be
performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will have a neurosensory assessment.
- Your performance status will be recorded.
- You will be asked about any symptoms and/or side effects you may be experiencing and
any drugs you may be taking.
- Blood (about 2 tablespoons) will be drawn for routine tests.
On Day 5 of Cycle 1 and Days 1 and 5 of Cycle 2, before you receive any of the study drugs,
blood (about 2 teaspoons each time) will be drawn to test for CIMP, a chemical "marker" in
the blood that may be related to how the drug may affect the cancer.
After every 3 cycles (Cycles 4, 7, 10 and so on), you will have a CT or MRI scan of the
chest, abdomen, and/or pelvis to check the status of the disease.
Length of Study:
You may continue to take the study drugs for as long as you are benefitting. You will be
taken off the study drugs if the disease gets worse, you experience any intolerable side
effects, or if the study doctor thinks it is in your best interest to stop taking the study
drugs.
If you chose to stop your participation in this study at any time, you should tell the study
doctor or study staff right away. They will make sure that proper procedures are followed
and a final visit is made for your safety.
End-of-Treatment Visit:
Within 10 days after your study treatment ends for any reason, you will return to the clinic
and the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will have a neurosensory assessment.
- Your performance status will be recorded.
- You will have a CT scan or MRI scan of the chest, abdomen, and/or pelvis to check the
status of the disease.
- You will be asked about any symptoms and/or side effects you may be experiencing and
any drugs you may be taking.
- Blood (about 2 tablespoons) will be drawn for routine tests.
Follow-Up:
The study doctor and study staff will follow your health status for the first 30 days after
you stop taking the study drugs to check if you are experiencing any treatment-related side
effects. The follow-up will be done during your regularly scheduled routine clinic visits
and/or by phone call, which should last about 5 minutes.
If you continue to experience any treatment-related side effects after the 30 days of
follow-up, the study staff will continue to follow up with you during your regularly
scheduled clinic visits until the side effects have gotten better or become stable.
Long-Term Follow-Up:
Every 3 months after the end-of-treatment visit, the study staff will contact you by phone
or email to check on how you are doing. If you are contacted by phone, the call should last
about 5 minutes. Your medical records may also be reviewed.
This is an investigational study. Azacitidine is FDA approved and commercially available
for myelodysplastic syndrome (MDS - a blood disease that often leads to cancer). Its use in
colorectal cancer is investigational.
Oxaliplatin and capecitabine are both FDA approved and commercially available as treatment
for colorectal cancer.
The use of azacitidine, oxaliplatin, and capecitabine in combination is investigational.
Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Azacitidine, and Capecitabine and Oxaliplatin (CAPOX)
Each first cycle (3 weeks)
Yes
Michael Overman, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Institutional Review Board
2009-0625
NCT01193517
August 2010
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |