A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Non-Small Cell Lung Cancer

Fecha de inicio: 1 de abril de 2004

Inclusion Criteria: * 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 * Performance status - ECOG 0-2 * Performance status - Karnofsky 60-100% * More than 12 weeks * Absolute neutrophil count \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * WBC \> 3,000/mm\^3 * AST and ALT =\< 2.5 times upper limit of normal (ULN) * Bilirubin =\< 1.5 times ULN * Creatinine =\< 1.5 times ULN * Creatinine clearance \>= 60 mL/min * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * 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 * No concurrent prophylactic growth factors (e.g., filgrastim \[G-CSF\] or epoetin alfa) * No more than 3 prior chemotherapy regimens * More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * 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 * Prior curative or palliative intent surgery allowed * At least 2 weeks since prior surgery and recovered * 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