Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment
Condition: Lymphoma; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Lymphoma; Intestinal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining more than one drug may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus
      phenylbutyrate in treating patients with advanced or metastatic solid tumors that have not
      responded to previous treatment.
    

Detailed description: 
      OBJECTIVES:

        -  Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with
           refractory solid tumors.

        -  Determine the maximum tolerated dose of this treatment regimen where maximal gene
           reexpression occurs in these patients.

        -  Evaluate the pharmacokinetics of these drugs in these patients.

        -  Determine the minimally effective dose of azacitidine in combination with phenylbutyrate
           that elicits a biological or clinical response in these patients.

      OUTLINE: This is a dose escalation study.

      Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV
      continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease
      progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine
      and phenylbutyrate until the maximum tolerated dose (MTD) is determined. The MTD is defined
      as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

      PROJECTED ACCRUAL: Approximately 3-50 patients will be accrued for this study within 12-18
      months.
    

Intervention name(s): Azacitidine Injection; sodium phenylbutyrate
Intervention type(s): Drug; Drug
Intervention description(s): subcutaneous injection (SC); continuous intravenous (CIV)
Other intervention name(s): AC; 5-AC
Intervention MeSH terms: Azacitidine; 4-phenylbutyric acid
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; recurrent adult Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; small intestine 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; recurrent adult T-cell leukemia/lymphoma; primary central nervous system non-Hodgkin lymphoma; intraocular lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; recurrent mantle cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma; stage III mycosis fungoides/Sezary syndrome; stage IV mycosis fungoides/Sezary syndrome; recurrent mycosis fungoides/Sezary syndrome; 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