Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: May 2, 2000
Last updated: March 13, 2010
Last verified: December 2005

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.

Condition Intervention Phase
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: azacitidine
Drug: sodium phenylbutyrate
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation to Maximally Tolerated Dose Trial of 5-Azacytidine (5 AC, NSC 102816) in Combination With Sodium Phenylbutyrate (PB, NSC 657802) in Patients With Refractory Solid Tumors

Resource links provided by NLM:

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

Study Start Date: June 2000
Detailed Description:


  • 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.


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


  • Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy

    • Lymphoma allowed
  • Progressive disease
  • Evaluable disease
  • No CNS metastases by CT scan or MRI



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Hemoglobin at least 8 g/dL (may be achieved by transfusion)
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin no greater than 2 mg/dL (unless due to hemolysis or Gilbert's syndrome)
  • SGOT and SGPT less than 2 times upper limit of normal


  • Creatinine no greater than 2.0 mg/dL


  • No active infection
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 2 weeks before, during, and 3 months after study participation


Biologic therapy:

  • Not specified


  • At least 4 weeks since prior adjuvant chemotherapy for advanced or metastatic disease and recovered

Endocrine therapy:

  • Not specified


  • At least 4 weeks since prior radiotherapy and recovered


  • Not specified
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Please refer to this study by its identifier: NCT00005639

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Study Chair: Michael A. Carducci, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications: Identifier: NCT00005639     History of Changes
Other Study ID Numbers: CDR0000067799, JHOC-99120302, JHOC-J9982, NCI-270
Study First Received: May 2, 2000
Last Updated: March 13, 2010
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
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

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Intestinal Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases
4-phenylbutyric acid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses processed this record on August 27, 2014