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Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer Clinical Trials Facts presented on Clinical Trials Search is not designed to be a substitute for certified medical advice, travels to or professional assistance by using a genuine doctor. We aren't mDs. Always consult your physician about Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer conditions. Clinical Trials Search.org is a website committed to listing clinical research studies in human subjects. Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer Clinical research trials and Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer health trials occur in a lot of of cities throughout the US. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials generally evaluate the potency of new does drugs. The role of the studies / undertakings is to figure out specific human healthcare questions. Clinical trials are a popular manner for mDs, government agencies, and private sector companies to locate treatments for all sorts of conditions, including Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer. Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer Clinical Trials and other clinical trials permit volunteers to get medical treatment choices before they are available to the general public. Many times the test subjects get professional assistance for free of charge, and occasionally they are compensated for their time. Sometimes there is a cost for a Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer clinical trial. Human subjects often get the best healthcare possible for their Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer condition. Risks are a reality, nevertheless, and could include additional or frequent dr. calls, medical hazards (perhaps life-threatening), and/or the treatment being ineffectual. Trials are federally governed with exacting guidelines to protect clinical trials patients.
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Home > "D" Clinical Trials Conditions > Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer  Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer
Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer
For Condition: Neoplasms
Status: Completed
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: This study will determine what dose of 5-fluorouracil (5-FU) can be given safely with leucovorin and UCN-01 to treat patients with cancer. 5-FU is used to treat many cancers. Leucovorin is a vitamin-like substance that boosts the cancer-fighting ability of 5-FU. UCN-01 is an experimental drug that has been shown to kill cancer cells in the test tube and shrink tumors in mice. Patients with cancer (other than blood cancers) that has spread throughout the body and for whom standard treatments are no longer effective may be eligible for this study. Patients with active heart or lung disease, or a history of diabetes requiring drug treatment may not participate. Candidates will be screened with a physical examination, blood and urine tests, electrocardiogram (EKG), and imaging studies, such as computed tomography (CT), magnetic resonance imaging (MRI) and chest X-rays to determine the extent of disease. Participants will receive 5-FU, leucovorin, and UCN-01 in 28-day treatment cycles as follows: on days 1, 8 and 15, leucovorin will be given by vein over 2 hours and 5-FU will be given by vein by a quick push into the vein 1 hour after the leucovorin was started. In addition, on days 1 through 3 of the first cycle, UCN-01 will be given by vein continuously for a total of 72 hours; in subsequent cycles it will be given continuously over days 1 and 2 for a total of 36 hours. No drug therapy will be given the last week of the cycle (days 22 through 28). UCN-01 will be given through a central venous line-a thin, plastic tube placed through the skin into one of the large veins in the neck or under the collarbone. This line can remain in place for months and can be used to administer drugs, transfuse blood, and draw blood samples. The doses of 5-FU and UCN-01 will be adjusted according to the side effects the patient experiences. Barring any serious side effects, all patients will undergo at least two treatment cycles. At the end of the second cycle, the response to treatment and drug side effects will be evaluated with blood tests and imaging studies. Patients whose tumor has grown during those 8 weeks will stop treatment. Patients whose tumor remains stable or shrinks will continue treatment as long as the cancer is under control and the side effects are tolerable. Safety and effectiveness evaluations in these patients will be repeated every 2 to 3 months. To determine the maximum safe dose of 5-FU that can be given with UCN-01, the 5-FU dose will be gradually increased in ensuing groups of patients. The first three patients will receive the starting dose; then, depending on the side effects, the dose may be gradually increased in subsequent groups of 3 to 6 patients. The leucovorin dose will remain constant in all patients. Patients may also be asked to undergo the following research procedures: -Periodic blood sampling to measure blood levels of the study drugs. -Bone marrow aspiration before starting therapy and 24 hours after the 5-FU dose in the second cycle to check the effects of therapy on growing cells. For this test, an area of skin over the hip is anesthetized and a special needle is used to draw bone marrow from the hipbone. -Tumor biopsy before treatment begins and once during treatment to examine the effects of the study drugs on tumor cells. A needle may be used to sample the tumor tissue or cancer cells may be obtained from fluid around the lungs or in the abdomen.
Details: The primary objective of this protocol is to determine the recommended dose of 5-fluorouracil (5-FU) which can be safely administered with fixed doses of leucovorin (LV) and the novel protein kinase C inhibitor, UCN-01. 5-FU will be administered weekly for three weeks followed by a one-week rest. Patients will begin treatment with an infusion of LV 500 mg/m(2) over 2 hours with a mid-infusion bolus of 5-FU. UCN-01 at 42.5 mg/m(2)/d will be given as a 72-hr continuous infusion for the first cycle, and then a maintenance infusion of 42.5 mg/m(2)/d will be given over 36 hours every 4 weeks. The initial 5-FU dose, 300 mg/m(2), is 50% of the recommended dose of 5-FU given with high-dose leucovorin on a weekly for 6 of 8 weeks schedule. The 5-FU dose will be escalated by 25% increments in cohorts of 3 patients until dose-limiting toxicity is observed in 2 patients. Dose adjustments will be made based on recognition of agent-specific toxicities and individual patient tolerance. Secondary objectives are to explore possible pharmacokinetic interactions between 5-FU and UCN-01, correlation of UCN-01 PK with alpha 1-acid glycoprotein levels , and the relationship between pharmacokinetic and clinical toxicity. In addition, the effects of this regimen on pertinent 5-FU (thymidylate synthase (TS) mRNA expression, TS protein content, extent of TS ternary complex formation) and potential UCN-01 (p21, Rb, PARP) pharmacodynamic endpoints will be assessed. Pharmacogenetic analysis of the polymorphism in the human thymidylate synthase gene will be performed to provide complementary information that is being collected in other current GI Tumor clinical protocols involving 5-FU base therapy.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: Patients must have histologically confirmed non-hematologic cancers that are metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Measurable disease is not required. Prior Treatment: The following criteria should be met: At least 4 weeks should have elapsed since prior chemotherapy/immunotherapy and the patients should have recovered from toxicities associated with the prior therapy. If patients received either mitomycin C or nitrosoureas at least 6 weeks must have elapsed. At least two weeks must have elapsed from prior radiation therapy, and patients should have recovered from radiation-associated toxicities. Patients should have recovered from prior surgery. ECOG performance status of 2 or better. Patients must have normal organ and marrow function as defined below: absolute neutrophil count greater than or equal to 1500/microL; platelets greater than or equal to 100,000/microL; total bilirubin less than or equal to 1.5 mg/dL; AST (SGOT)/ALT (SGPT) less than or equal to 3 times institutional upper limit of normal; and creatinine less than or equal to 1.5 mg/dL OR a creatinine clearance greater than or equal to 60 mL/min for a BSA of 1.73 m(2). Ability to understand and the willingness to sign a written informed consent document. Age greater than or equal to 18 years. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. EXCLUSION CRITERIA: A history of unusually severe and/or prolonged toxicity during prior therapy with 5-FU or 5-FU prodrugs. Patient is receiving other investigational agents. Patients with brain metastasis or primary CNS malignancy will be excluded from this clinical trial. Patients with known, active coronary artery disease or pulmonary dysfunction will be excluded. Patients with symptoms suggestive of coronary artery disease will be investigated by a cardiologist prior to enrollment. Those patients with evidence of active cardiac or pulmonary disease will be excluded. Patients with prior pulmonary/mediastinal radiation exceeding 40 Gy will be excluded from this trial. Patients with diabetes mellitus requiring either insulin or oral hypoglycemic therapy will be excluded. A serious concurrent medical illness that, in the opinion of the investigators, might place the patient at increased risk of toxicity if they were to receive the cheomotherapy program outlined in this protocol. Ongoing or active infection requiring IV antibiotics. Psychiatric illness or social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because UCN-01 has the potential for teratogenic or abortifacient effects. HIV positive patients are excluded. Patients receiving systemic corticosteroid therapy are excluded.
Total Enrollment: 24
Location and Contact Information:
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
United States
Additional Information:
Study ID Numbers: 020222; 02-C-0222
Study Start Date: May 31, 2002
Record last reviewed: July 9, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00039637
Other Neoplasms Studies:
1. A Phase I Trial of 5-Flouroucacil Given with 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients with Solid Tumors
2. Phase I Study of Anakinra to Treat Advanced Cancers that Produce Interluekin-1
3. Treatment of neutropenic patients with fever who are suspected to have a gram positive infection (a specific kind of bacteria)
4. Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer
5. A Phase I, Open Label, Dose Escalation Study of a New Formulation of Calcitriol (DN-101) for Safety, Tolerability, and Pharmacokinetics in Patients with Advanced Malignancies
Related Studies:
Other Neoplasms Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Dose Determination of 5-Fluorouracil in Combination with Leucovorin and the Experimental Drug UCN-01 to Treat Cancer
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