RATIONALE: Drugs used in chemotherapy, such as decitabine and valproic acid, work in 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 decitabine and valproic acid in treating patients with non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
recurrent non-small cell lung cancer stage IV non-small cell lung cancer	Drug: decitabine  Drug: valproic acid  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the safety and tolerability of decitabine and valproic acid in patients with non-small cell lung cancer.
• Determine the recommended phase II dose of this regimen in these patients.

Secondary

• Determine the ability of this regimen to lead to biological changes in tumor and surrogate tissues in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV over 1 hour on days 1-10 and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of decitabine and valproic acid until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, an additional 6 patients are treated at that dose.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 12.5 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer
• Tumor accessible to biopsy by bronchoscopy, through surface biopsy (e.g., skin punch biopsy for skin/subcutaneous metastasis) or through CT scan guidance
• Not eligible for curative surgery, chemotherapy, radiotherapy, or multimodality treatment options
• No uncontrolled brain metastases
• Controlled brain metastases allowed provided patient has no neurologic deterioration when off steroids; has completed prior radiotherapy or other treatments; has fully recovered from prior treatment; and does not require anticonvulsants

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• WBC > 3,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction to compounds of similar chemical or biological composition to decitabine, valproic acid, or other study agents
• No other concurrent uncontrolled illness
• No ongoing or active infection requiring antibiotics
• No history of seizures requiring anticonvulsants
• No medical problem that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Chemotherapy
• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or epoetin alfa)

Chemotherapy

• No more than 3 prior chemotherapy* regimens
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered NOTE: *Chemotherapy includes molecular targeted agents, such as epidermal growth factor receptor antagonists, standard (or investigational) cytotoxic agents with or without antibodies, or other novel agents

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• Prior definitive radiotherapy to the chest allowed
• Clinical (radiographic or other) evidence of tumor progression for previously irradiated indicator lesion in the chest
• More than 2 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy

Surgery

• Prior curative or palliative intent surgery allowed
• At least 2 weeks since prior surgery and recovered

Other

• At least 4 weeks since prior photodynamic therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents
• No concurrent administration of any of the following medications:
• Aspirin
• Chronic low-dose (≤ 81 mg/day) aspirin allowed
• Felbamate
• Rifampin
• Amitriptyline
• Nortriptyline
• Carbamazepine
• Clonazepam
• Diazepam
• Ethosuximide
• Lamotrigine
• Phenobarbital
• Barbiturates
• Primidone
• Phenytoin
• Zidovudine
• No concurrent divalproex sodium
• Concurrent gabapentin for neuropathic pain allowed

Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210,  United States; Recruiting

Study chairs or principal investigators

Gregory A. Otterson, MD,  Principal Investigator,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000367115; OSU-0346; OSU-2003C0087; NCI-6237; NCT00084981
Record last reviewed:  February 2005
Last Updated:  March 15, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084981
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08