|
Reactivating Tumor Suppressor Genes
Untitled Document
Name of the Trial
Phase I Study of 5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Patients
With Advanced Solid Tumors (NCI-06-C-0221). See the protocol
summary.
Principal Investigator
Dr. James Doroshow, NCI Center for Cancer Research and Division of Cancer Treatment and Diagnosis.
 |
Dr. James Doroshow
Principal Investigator |
Why This Trial Is Important
A drug called 5-fluoro-2'-deoxycytidine (FdCyd) may be effective in blocking
a cellular process called DNA methylation, which is believed to play an important
role in the development of many cancers. Excessive methylation (hypermethylation)
may silence, or "turn off," genes that suppress tumor formation, thereby
allowing abnormal cells to proliferate.
Preclinical studies have shown, however, that FdCyd is rapidly broken down
in the body, and the breakdown products do not block methylation. Another drug
called tetrahydrouridine (THU) may help prevent FdCyd breakdown when administered
with it. THU may allow FdCyd to remain intact long enough to reduce the hypermethylation
of tumor suppressor genes and possibly allow them to be reactivated.
This is the first clinical trial to test the combination of FdCyd and THU in
humans. Researchers are interested in establishing the maximum tolerated dose
and determining how this regimen affects the methylation of certain genes. They
will also determine the toxicity of this treatment, and examine its effects
on levels of proteins that are important for the progression of cancer.
"FdCyd/THU is being developed collaboratively by researchers at the City
of Hope Comprehensive Cancer Center and the NCI," said Dr. Doroshow. "So
far, patients in the trial have tolerated the combination well, and we have
seen some clinical responses.
"Our hope is to develop the regimen as an orally available combination
that will safely and effectively deliver repetitive doses of these tumor-suppressor
gene-activating agents to patients."
Who Can Join This Trial
Researchers will enroll up to 60 adult patients with advanced solid tumors
that have not responded to standard treatment. Patients with breast cancer will receive higher priority for accrual. See the list
of eligibility criteria.
Study Sites and Contact Information
This study is taking place at the NIH Clinical Center in Bethesda, Md, and
at study sites in California. See the list
of study contacts or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937.
The toll-free call is confidential.
 Back to Top |
