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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

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


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.

Inclusion 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

- 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Michael A. Carducci, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02250

NCT ID:

NCT00002909

Start Date:

February 1997

Completion Date:

Related Keywords:

  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Neoplasms

Name

Location

Johns Hopkins Oncology CenterBaltimore, Maryland  21287