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Sponsors and Collaborators: |
Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00002909 |
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectivenes of phenylbutyrate in treating adults with refractory solid tumor or lymphoma.
Condition | Intervention | Phase |
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Lymphoma Unspecified Adult Solid Tumor, Protocol Specific |
Drug: chemotherapy Drug: oral sodium phenylbutyrate |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A PHASE I CLINICAL AND PHARMACOLOGIC EVALUATION OF PHENYLBUTYRATE IN PATIENTS WITH REFRACTORY SOLID TUMORS: STUDY OF CONTINUOUS EXPOSURE ORAL PHENYLBUTYRATE ON A THREE TIMES DAILY SCHEDULE |
Study Start Date: | February 1997 |
OBJECTIVES: I. Determine the maximum tolerated dose of oral phenylbutyrate that can be given three times daily in patients with refractory solid tumors or lymphoma until disease progression or a trough plasma concentration of 2-6 micromoles per liter is achieved. II. Characterize the pharmacokinetics of oral phenylbutyrate absorption, and determine whether there is time dependence in the systemic clearance rate during multiple dosing. III. Seek preliminary evidence of therapeutic activity of phenylbutyrate when administered on this schedule in these patients. IV. Correlate any observed responses and toxic effects with results of bioassays and tissue sampling for phenylbutyrate activity.
OUTLINE: This is a dose-seeking study. All patients receive oral phenylbutyrate three times daily. Groups of 4 or more patients receive escalating doses of phenylbutyrate until the maximum tolerated dose (MTD) is determined.
Treatment continues until disease progression or unacceptable toxicity intervenes.
PROJECTED ACCRUAL: At least 4 patients are studied at each dose level. An additional 20 patients will be accrued at the maximum tolerated dose.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor or lymphoma that is progressive or refractory to conventional therapy or for which no effective therapy is known Priority given to hormone-refractory prostate cancer and melanoma No untreated CNS metastases Head CT not required in the absence of clinical signs or symptoms but recommended for metastatic melanoma
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC greater than 2,000/mm3 OR Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin less than 1.5 mg/dL AST/ALT less than 1.5 times normal Renal: Creatinine less than 2.0 mg/dL Obstructive uropathy allowed if relieved by nephrostomy or other appropriate device Cardiovascular: Left ventricular ejection fraction greater than 40% by MUGA or normal by echocardiogram No history of congestive heart failure No uncontrolled hypertension (diastolic greater than 110 mm Hg) Pulmonary: Forced expiratory volume (1 second) greater than 1.5 L/min Other: No active infection, including HIV or viral hepatitis No active seizure disorder No clinical evidence of increased intracranial pressure No baseline dementia (mini-mental exam less than 23) No autoimmune disease, including systemic lupus erythematosus, scleroderma, or other connective tissue illness No nonmalignant medical or psychiatric problem of sufficient severity to limit full compliance with study or to pose undue risk Not pregnant or nursing Adequate contraception required of fertile patients for 2 weeks prior to, during, and for 3 months after study Normal gastrointestinal function with ability to tolerate large intake of oral volume required for phenylbutyrate administration Patients with persistent nausea or moderate to severe anorexia may not be good candidates for study
PRIOR CONCURRENT THERAPY: Fully recovered from all prior therapy Biologic therapy: Prior suramin allowed if serum suramin level less than 50 micrograms/mL at entry Chemotherapy: At least 28 days since chemotherapy No prior phenylacetate, phenylbutyrate, or antineoplaston therapy Endocrine therapy: The following may be continued during study: Luteinizing hormone-releasing hormone agonist with evidence of tumor progression (e.g., rising prostate-specific antigen, new lesions on bone scan) despite therapy Adrenal steroid replacement (if needed) Dexamethasone or other steroids At least 4-6 weeks since flutamide with evidence of PSA progression required (if possible) Radiotherapy: At least 28 days since radiotherapy Surgery: At least 28 days since major surgery
United States, Maryland | |
Johns Hopkins Oncology Center | |
Baltimore, Maryland, United States, 21287 |
Study Chair: | Michael A. Carducci, MD | Sidney Kimmel Comprehensive Cancer Center |
Study ID Numbers: | CDR0000065274, J-9616, JHOC-9616, NCI-T95-0017H |
Study First Received: | November 1, 1999 |
Last Updated: | February 6, 2009 |
ClinicalTrials.gov Identifier: | NCT00002909 History of Changes |
Health Authority: | United States: Federal Government |
stage III adult Hodgkin lymphoma stage IV adult Hodgkin lymphoma recurrent adult Hodgkin lymphoma unspecified adult solid tumor, protocol specific stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III adult diffuse small cleaved cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse large cell lymphoma stage III adult immunoblastic large cell lymphoma stage III adult lymphoblastic lymphoma stage III adult Burkitt lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma |
stage IV grade 3 follicular lymphoma stage IV adult diffuse small cleaved cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse large cell lymphoma stage IV adult immunoblastic large cell lymphoma stage IV adult lymphoblastic lymphoma stage IV adult Burkitt lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma |
Lymphoma, Mantle-Cell Lymphoma, Follicular Mantle Cell Lymphoma Lymphoma, B-Cell, Marginal Zone Lymphoblastic Lymphoma Follicular Lymphoma Lymphoma, Large-cell, Immunoblastic Lymphoma, B-Cell Lymphoma, Small Cleaved-cell, Diffuse Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, T-Cell Lymphoma, Large-Cell, Immunoblastic Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-cell |
Leukemia, B-cell, Chronic Hodgkin Disease Lymphoma Lymphoma, Large B-Cell, Diffuse Immunoproliferative Disorders 4-phenylbutyric acid Hodgkin Lymphoma, Adult Leukemia-Lymphoma, Adult T-Cell Immunoblastic Lymphadenopathy Hodgkin's Disease Recurrence Burkitt's Lymphoma Lymphatic Diseases Chronic Lymphocytic Leukemia B-cell Lymphomas |
Lymphatic Diseases Neoplasms Immunoproliferative Disorders Neoplasms by Histologic Type Immune System Diseases Antineoplastic Agents |
4-phenylbutyric acid Therapeutic Uses Lymphoproliferative Disorders Lymphoma, Non-Hodgkin Lymphoma Pharmacologic Actions |