Track topics on Twitter Track topics that are important to you
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
Primary Objectives To evaluate the safety and activity of administering a combination of two antineoplastic agents, erlotinib and 5-azacytidine, in an effort to inhibit multiple operative ...
This phase II trial will evaluate, in first line advanced or metastatic gastric cancer, the efficacy and tolerance of another oxaliplatin, 5FU bolus combination already tested in advanced...
This study seeks to determine the optimum dose frequency of 5-Azacytidin (5-AZA) infusions into the fourth ventricle of the brain. The study's primary objective is to establish the maximum...
Primary objective : To compare the combination of S-1 and oxaliplatin(SOX) to the combination of capecitabine and oxaliplatin(COX) therapy for advanced or metastatic colorectal carcinoma....
To investigate the therapy effect and security of oxaliplatin and fluorouracil on with or without concomitant vascular invasion and extrahepatic metastases unresectable advanced primary li...
There is no single standard chemotherapy regimen for elderly patients with advanced gastric cancer (AGC). A phase III trial has confirmed that both capecitabine monotherapy and capecitabine plus oxali...
Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase 2 trial (ATTRACTION-4).
Nivolumab is approved as an option for third- or later-line treatment for advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the ther...
The German rectal cancer trial CAO/ARO/AIO-04 has shown a significant benefit in 3-year disease-free survival (DFS) of adding oxaliplatin to a standard preoperative 5-fluorouracil-based chemoradiother...
To evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).
The standard strategy for locally advanced lower rectal cancer is chemoradiotherapy followed by total mesorectal excision (TME) in Western countries and TME followed by adjuvant chemotherapy without p...
An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer.
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
Advanced technology that is costly, requires highly skilled personnel, and is unique in its particular application. Includes innovative, specialized medical/surgical procedures as well as advanced diagnostic and therapeutic equipment.
A cancer registry mandated under the National Cancer Act of 1971 to operate and maintain a population-based cancer reporting system, reporting periodically estimates of cancer incidence and mortality in the United States. The Surveillance, Epidemiology, and End Results (SEER) Program is a continuing project of the National Cancer Institute of the National Institutes of Health. Among its goals, in addition to assembling and reporting cancer statistics, are the monitoring of annual cancer incident trends and the promoting of studies designed to identify factors amenable to cancer control interventions. (From National Cancer Institute, NIH Publication No. 91-3074, October 1990)
An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...