Phenylbutyrate in Treating Patients With Refractory Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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Phase I trial to study the effectivenes of phenylbutyrate in treating adults with refractory solid tumor or lymphoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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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.

Official Title
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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

Conditions
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Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: chemotherapy
* Drug: oral sodium phenylbutyrate


Participation Criteria
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Eligibility Criteria
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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 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 Bilirubin less than 1.5 mg/dL AST/ALT less than 1.5 times normal Creatinine less than 2.0 mg/dL Obstructive uropathy allowed if relieved by nephrostomy or other appropriate device 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) Forced expiratory volume (1 second) greater than 1.5 L/min 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 Prior suramin allowed if serum suramin level less than 50 micrograms/mL at entry At least 28 days since chemotherapy No prior phenylacetate, phenylbutyrate, or antineoplaston 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) At least 28 days since radiotherapy At least 28 days since major surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: chemotherapy<br> <br> Drug: oral sodium phenylbutyrate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, 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, recurrent adult Burkitt lymphoma