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Home > "P" Clinical Trials Conditions > Phase I: UCN-01 and Prednisone  Phase I: UCN-01 and Prednisone
Phase I: UCN-01 and Prednisone
For Condition: Tumor,Lymphoma
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: Prednisone is often used to treat lymphoma and other cancers. The use of UCN-01, another anticancer agent, has been studied in humans since 1996 and has been shown to be effective in treating some lymphomas. The objective of this study is to determine 1) the side effects of the two drugs in combination, 2) the optimal dose of UCN-01 with prednisone, and 3) the efficiency of using them in combination. Due to the experimental nature of this study, however, it may or may not benefit patients. The study will enroll patients over age 18 who have either a solid tumor or lymphoma. Patients should have had their last dose of chemotherapy or radiation at least 4 weeks before beginning the study (6 weeks for certain chemotherapy agents) and should have recovered from the toxicities of those treatments. Three patients will be initially entered at a predetermined UCN-01 dose level. The initial group will receive the lowest. New groups of patients, who will start at higher doses of UCN-01, will be enrolled at 4-week intervals until dose-limiting toxicities are determined. The treatment will be given in 28-day cycles. During the first 5 days of each cycle, patients will receive oral prednisone. On day 3, they will receive UCN-01 intravenously through a central venous catheter. For the first cycle, UCN-01 will be given over 72 hours; for the remaining cycles, it will be given over 36 hours. It will be given using a portable infusion device so the patients will have more mobility. The first two cycles will require approximately 7 hospital days so patients can be closely monitored. The remaining cycles can be on an outpatient basis, although patients will need to be in the area of the National Institutes of Health while receiving the UCN-01 infusion. Before enrolling patients in the study, the researchers will take a medical history and do a physical exam, blood work, radiological tests, pulmonary function tests, urine tests, and possibly bone marrow tests, if appropriate, to evaluate each patient's cancer and overall health. Patients who do not already have a central venous catheter will have one installed.
Details: Previous clinical experience with UCN-01 has suggested activity in lymphoma and in vitro data suggests synergy is possible with other cytotoxic chemotherapeutic agents. For these reasons it is of interest to combine UCN-01 with anti-lymphoma regimens in future clinical trials. Many such regimens include prednisone (i.e. EPOCH, CHOP) and given that hyperglycemia was a dose limiting toxicity of UCN-01 in initial Phase I trials, it is prudent to first discover the toxicities and maximally tolerated dose of the UCN-01 and prednisone combination prior to combining UCN-01 to prednisone containing anti-lymphoma regimens. This trial will provide information necessary for further development of UCN-01 in prednisone containing chemotherapy strategies. In addition to following toxicities, monitoring the pharmacokinetic profile of this combination will be important. Earlier Phase I trials with UCN-01 alone demonstrated unexpectedly higher plasma concentrations of UCN-01 and a prolonged half-life. Subsequent in vitro and in vivo animal experiments determined the likely etiology was high affinity binding to a human plasma protein, alpha-1-acid glycoprotein (hAAG). Prednisolone, the active metabolite of prednisone, also binds to hAAG and may raise the active, unbound (free) fraction of UCN-01 by competitively binding to the plasma protein. Higher levels of 'free' UCN-01 may exacerbate the hyperglycemic and pulmonary toxicities seen in single agent UCN-01. In addition, the hyperglycemic effect of prednisone may add to that of UCN-01. Conversely, prednisone may ameliorate the pulmonary toxicities by the ability of glucocorticoids to inhibit nitric oxide synthase. Therefore, the main goal of combining prednisone with UCN-01 is to discover the toxicities and maximally tolerated dose of the combination. Ancillary goals will be to assess changes in the pharmacokinetics of UCN-01 and to determine the effect of the combination on nitric oxide production.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: Histologic diagnosis of a solid tumor or lymphoma confirmed by the Laboratory of Pathology, NCI. Has already received standard therapy for their malignancy and disease has progressed on this therapy and no other therapies are likely to improve survival. Age greater than or equal to 18 years. Prognosis of 3 months or greater. Patients must have normal organ and marrow function as defined below: Total Bilirubin less than or equal to 1.5 x ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome; AST less than or equal to 2.5 x ULN, ALT less than or equal to 2.5 X ULN; Creatinine clearance greater than 60 ml/min (measured via 24 hour urine specimen) or serum creatinine less than or equal to 1.5 mg/dl; Absolute neutrophil count greater than 1000/mm(3); Platelet count greater than 100,000/mm(3); 12hr fasting glucose less than or equal to 110 mg/dl OR less than or equal to 140 mg/dl AND Hemoglobin A1C less than or equal to 6.5 mg/dl; PT/PTT less than or equal to 1.5 x ULN. DLCO greater than or equal to 70% of predicted (corrected for anemia, if present), FEV1 greater than or equal to 75% of predicted. ECOG Performance Status 0-2. Patient able to understand and sign an informed consent document. Patient able and willing to follow guidelines of clinical protocol including visits to NCI, Bethesda, Maryland for treatment and follow up visits. Last dose of chemotherapy or radiation therapy was greater than 4 weeks (6 weeks for nitrosourease and mitomycin C) prior to commencement of this protocol and patient has recovered from any toxicities associated with those treatments. Prostate cancer patients must have progressed through hormonal therapy with GnRH agonists and withdrawal of testosterone receptor antagonists. They must continue GnRH agonist during the trial (if orchiectomy was not performed) and have castrate testosterone levels prior to starting. The effects of UCN-01 on the developing human fetus are unknow therefore women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier methods) during the study and for a period of 2 months after the last dose of UCN-01 (due to the long half life of this drug). EXCLUSION CRITERIA: Due to the tendency of UCN-01 to cause hyperglycemia, patients with a history of diabetes or hyperglycemia within the last 1 year that requires/required a diabetic diet, oral hypoglycemics, or insulin. Uncontrolled illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, seizure disorder, or psychiatric illness that may limit compliance with study requirements. These illnesses may also be exacerbated by UCN-01 and/or prednisone. Patients with a history of interstitial lung disease within the last 1 year will be excluded because of the pulmonary toxicities seen with UCN- 01. Patients who have required oxygen therapy for hypoxia due to any cause in the last 6 months will be excluded because of the pulmonary toxicities seen with UCN-01. Requires oral or IV steroid therapy for any reason as this will interfere with the primary objectives of this study. Positive serology for HIV because of the increased risk for lethal infections in immunocompromised patients treated with steroids. Local complications from disease requiring urgent therapy (i.e. hydronephrosis, spinal cord compression, severe pain requiring improved pain management). Major surgery within the last 21 days. Brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities. Pregnancy. Lactating women who are breast feeding. Diagnosis of duodenal or gastric ulcer or severe gastritis within the 6 months prior to therapy inception due to the risk of exacerbation of these conditions with prednisone. Prior treatment with UCN-01. Use of other investigational agents within 4 weeks of on study date. History of allergic reactions to other indolocarbazoles.
Total Enrollment: 24
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 020241; 02-C-0241
Study Start Date: July 14, 2002
Record last reviewed: April 15, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00041873
Other Lymphoma Studies:
1. Graft-Versus-Host Disease in Treating Patients With Recurrent or Refractory Lymphoma or Hodgkin's Disease
2. Bryostatin 1 Plus Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed Indolent Non-Hodgkin's Lymphoma
3. Selective T-Cell Depletion to Reduce Graft-Versus-Host-Disease in Patients Receiving Stem Cell Transplantation to Treat Leukemia, Lymphoma or Myelodysplastic Syndromes
4. Yttrium Y 90 SMT 487 in Treating Patients With Refractory or Recurrent Cancer
5. Chemotherapy Plus Donor White Blood Cell Infusion in Treating Patients With Relapsed Hematologic Cancer Following Donor Peripheral Stem Cell Transplantation
Related Studies:
Other Lymphoma Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Phase I: UCN-01 and Prednisone
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