MTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer

Inclusion criteria

• Written Informed Consent.
• Males or females.
• 18-75 years.
• Histologically or cytologically confirmed non-estrogen dependent advanced solid malignancy who has failed standard therapies and/or for which no curative therapeutic option exists (phase I) or ;
• Histologically or cytologically confirmed NSCLC of stage IIIb or IV (phase IIa) that has failed or is ineligible to standard therapies.
• One or more tumor lesions measurable by RECIST criteria
• Life expectancy of at least 3 months.
• ECOG performance of 2 or less.

Exclusion criteria

• Prior decitabine or genistein therapy.
• Received cytotoxic agent, hormonal therapy, radiation therapy, or other targeted cancer therapies or investigational agent within 4 weeks prior to study entry.
• Patients with confirmed estrogen receptor-positive cancers, or patients with a primary breast or endometrial cancer for which phenotyping analysis has not been performed.
• Presence of uncontrolled brain metastases or leptomeningeal disease.
• Uncontrolled cardiovascular disorders, including symptomatic heart failure, unstable angina and cardiac arrhythmias.
• Inadequate baseline organ function as shown by following laboratory values :

• Hemoglobin < 90 g/L
• Absolute neutrophil count < 1,500 /microliter
• Platelet count < 100,000 /microliter
• Total bilirubin > 1.5 ULN
• AST and ALT > 2.5 ULN
• Creatinine clearance < 60 ml/min
• To be dependent of oxygen treatment.
• Active infections requiring antibiotics.
• Pregnancy or breastfeeding. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy.
• Known allergic reactions to soy derivatives or deoxycytidine derivatives.
• Active alcohol or drug abuse.
• Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduces the probability of assessing clinical effect.
• Other malignancies diagnosed within the last 5 years with the exception of Basal Cell Carcinoma of the skin.
• Gastrointestinal disorders or abnormalities that may interfere with the absorption of genistein.
• Patients unable to comply with the study protocol and follow-up schedule for any psychological, familial, sociological or geographical reason.