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The goal of this clinical research study is to find the highest safe dose of a combination of 5-azacytidine and oxaliplatin (a platinum-based chemotherapy drug) that can be given to patients with advanced cancer who have already been treated with platinum drugs. Researchers want to study the interaction of 5-azacytidine in combination with oxaliplatin, to find out if this can reverse a patient's resistance to platinum-based drugs.
Both 5-azacytidine and oxaliplatin are FDA approved. However, the combination of the drugs together is investigational.
The Study Drugs 5-Azacytidine is designed to activate ("turn on") certain genes in cancer cells whose job is to fight tumors.
Oxaliplatin is designed to block the growth and spread of new cancer cells, eventually destroying them. It is designed to kill cancer cells by damaging their DNA (the genetic material of cells).
Standard anti-nausea medications will be given to try to prevent stomach/intestinal side effects. This will be up to the attending doctor.
Study Groups and Study Drug Administration:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of 5-azacytidine and oxaliplatin, based on when you joined this study. Up to 6 dose levels of 5-azacytidine and oxaliplatin will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the drug combination is found.
Once the highest tolerable dose is found, up to an additional 20 participants, with colorectal cancer, called the "Expansion Phase," will receive the study drugs at that dose, to further study the safety of the drugs. There are no differences in study procedures except only the Expansion Phase will have biopsies and blood-clotting tests.
You will receive the following study drugs during every 28-day study cycle:
On Days 1-5 of every 28-day cycle, you will receive 5-azacytidine through a needle and catheter in your vein over about 15-30 minutes.
On Days 2-5, you will also receive oxaliplatin by vein over about 2 hours.
While you are receiving the study drugs, you will have the following study tests performed:
- Every 1-2 weeks for the first cycle, then every 4 weeks after that, you will have a physical exam and your vital signs will be checked.
- On Days 1, 5, and 12 of Cycle 1, you will have blood (about 2 teaspoons) drawn for pharmacogenetic (PGt) testing. PGt testing looks at how someone's genes may influence if and how well the study drug may affect the disease.
- During the first week of every cycle, you will have your weight and performance status checked.
Every week while you are on study, you will have blood (about 2 teaspoons) drawn for routine tests.
- Every week while you are on study, you will be asked about any side effects you may be experiencing.
- You will have a PET scan, CT scan, MRI, or X-ray performed at Week 8, and every 8 weeks after that, to check the status of the disease.
- At Week 8, and every 8 weeks after that, blood (about 1 tablespoon) will be drawn for tumor marker testing.
- If you are in the expansion phase, on Day 12 (+/- 1 day) of the first cycle, you will have blood (about 1 teaspoon) drawn to see how your blood clots.
- If you are in the expansion phase, you will have 2 tumor biopsies performed for research purposes to see how your genes change with therapy. These samples will be studied to look for special markers that may help researchers better understand the relationship between 5-azacytidine, oxaliplatin, and cancer. The first biopsy will be performed during screening, before your first dose of the study drugs. The next biopsy will be performed on Day 12 (+/- 1 day) of the first cycle. To collect a tumor biopsy, the affected area is numbed with anesthetic, and a small amount of tumor tissue is withdrawn through a large needle.
Pharmacokinetics (PK) Testing:
Extra blood (about 2 teaspoons each time) will be drawn for a non-routine (research) test called pharmacokinetic (PK) testing. PK testing measures the amount of study drug(s) in the body at different time points.
5-Azacytidine: On Day 1 and Day 5 of Cycle 1, you will have 11 PK blood samples drawn. They will be drawn before treatment, at the end of the dose, and then at 5, 10, 15, 30, 60, 90 minutes, and at 2, 3, and 6 hours after the end of the dose.
On Day 2 of Cycle 1, you will have 9 PK blood samples drawn. They will be drawn before treatment, at the end of your dose, and then at 1, 2, 4, 6, 8, 12 and 24 hours (before the Day 3 dose).
Once the highest tolerable dose is found, up to an additional 20 participants, with colon cancer, called the "Expansion Phase," will receive the study drugs at that dose, to further study the safety of the drugs.
There are no differences in study procedures except only the Expansion Phase will have biopsies and blood-clotting tests.
Length of Study:
You may stay on study for up to 6 cycles. You will be taken off-study early if the disease gets worse, intolerable side effects occur, or if you decide to come off study.
Once you are no longer receiving the study drugs, you will have an end-of-study visit. At this visit, you will have a physical exam, including measurement of your vital signs, weight, and performance status. Blood (about 2 teaspoons) will be drawn for routine tests, and you will be asked about any side effects you may be experiencing.
This is an investigational study. 5-azacytidine and oxaliplatin are FDA approved for certain cancer types and are commercially available. At this time, this drug combination is being used in research only.
Up to 56 patients may participate in this study. All will be enrolled at M. D. Anderson.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
Published on BioPortfolio: 2014-07-24T14:10:30-0400
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