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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 ³.

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 ⁴.

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 ⁵ or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The toll-free call is confidential.

Glossary Terms

The amount of medicine taken, or radiation given, at one time.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A substance that makes tumor cells more sensitive to radiation therapy and is being studied in the treatment of cancer. It belongs to the families of drugs called cytidine deaminase inhibitors, multidrug resistance modulators, and radiosensitizers.

The extent to which something is poisonous or harmful.

A type of gene that makes a protein called a tumor suppressor protein that helps control cell growth. Mutations (changes in DNA) in tumor suppressor genes may lead to cancer. Also called antioncogene.