RATIONALE: Drugs used in chemotherapy, such as decitabine, work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of decitabine in treating patients who have metastatic or unresectable refractory solid tumors or lymphomas.

Condition	Treatment or Intervention	Phase
adult solid tumor Leukemia Lymphoma small intestine cancer	Drug: decitabine  Procedure: chemotherapy	Phase I

OBJECTIVES: Primary

• Determine the maximum tolerated dose of decitabine in patients with advanced refractory solid tumors or lymphomas.
• Determine the toxicity of this drug in these patients.
• Determine the dose of this drug at which tumor DNA demethylation is optimal in these patients.
• Determine the dose of this drug at which peripheral blood mononuclear cell demethylation is optimal in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Correlate plasma concentrations with hypomethylation effects of this drug in these patients.

Secondary

• Determine, preliminarily, the efficacy of this drug, in terms of objective response, in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of decitabine 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 toxicity.

PROJECTED ACCRUAL: A total of 6-36 patients will be accrued for this study within 1-18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy
• Solid tumor or lymphoma
• Metastatic or unresectable disease
• Standard curative or palliative therapies do not exist or are no longer effective
• Received ≥ 1 prior chemotherapy regimen
• No maximum number of prior regimens
• Tumor accessible for repeat biopsy
• No known brain metastases unless the following criteria are met:
• Previously treated with cranial irradiation
• No requirement for > 8 mg of dexamethasone (or other equivalent steroid) per day to maintain a performance status ECOG 0-1 AND steroid dose has not increased within the past 2 weeks
• No seizure (focal or generalized) within the past 3 weeks
• No requirement for enzyme-inducing anti-convulsants

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 (0-1 for patients with brain metastases) OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 140,000/mm^3

Hepatic

• Bilirubin ≤ 1.0 mg/dL
• AST and ALT ≤ 1.5 times upper limit of normal
• INR normal
• PTT normal

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No potentially life-threatening cardiac arrhythmia
• Systolic blood pressure 90-160 mm Hg
• Diastolic blood pressure 50-110 mm Hg

Other

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy (1 week for palliative low-dose radiotherapy to the limbs provided pelvis, ribs, sternum, scapulae, vertebrae, and skull were outside of the radiotherapy field) and recovered

Surgery

• More than 2 weeks since prior surgery

Other

• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

David James Stewart, MD, FRCPC,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000378040; MDA-2004-0040; NCI-6533
Record last reviewed:  September 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089089
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17