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Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment
This study has been completed.
First Received: May 2, 2000   Last Updated: July 23, 2008   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: NCT00005639
  Purpose

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
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: azacitidine
Drug: sodium phenylbutyrate
Phase I

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: Azacitidine Sodium phenylbutyrate
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

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

Study Start Date: June 2000
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.

  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 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • 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

Hepatic:

  • 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

Renal:

  • Creatinine no greater than 2.0 mg/dL

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

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

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005639

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

Additional Information:
No publications provided

Study ID Numbers: CDR0000067799, JHOC-99120302, JHOC-J9982, NCI-270
Study First Received: May 2, 2000
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00005639     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
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

Study placed in the following topic categories:
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Ileal Diseases
Follicular Lymphoma
Duodenal Neoplasms
Mycoses
Leukemia, Lymphocytic, Chronic, B-Cell
Azacitidine
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Digestive System Neoplasms
4-phenylbutyric acid
B-cell Lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Antimetabolites
Gastrointestinal Diseases
Lymphoma, Follicular
Central Nervous System Lymphoma, Primary
Lymphoma, B-Cell, Marginal Zone
Sezary Syndrome
Mycosis Fungoides
Lymphoblastic Lymphoma
Lymphoma, Large-cell, Immunoblastic
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Ileal Diseases
Duodenal Neoplasms
Neoplasms by Site
Ileal Neoplasms
Jejunal Diseases
Therapeutic Uses
Azacitidine
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Digestive System Neoplasms
Immune System Diseases
4-phenylbutyric acid
Enzyme Inhibitors
Intestinal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Lymphatic Diseases
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on May 07, 2009