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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


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

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael A. Carducci, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000067799

NCT ID:

NCT00005639

Start Date:

June 2000

Completion Date:

Related Keywords:

  • Lymphoma
  • Small Intestine Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Neoplasms
  • Intestinal Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410