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Phenylbutyrate in Treating Patients With Refractory Solid Tumors or Lymphoma
This study has been completed.
First Received: November 1, 1999   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002909
  Purpose

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
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: February 1997
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002909

Locations
United States, Maryland
Johns Hopkins Oncology Center
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Michael A. Carducci, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Carducci M, Bowling MK, Eisenberger M, et al.: Phenylbytyrate (PB) for refractory solid tumors: Phase I evaluation of continuous oral PB exposure. [Abstract] Proc Am Assoc Cancer Res 39: A507, 1998.

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

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
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

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on September 01, 2009