Inclusion Criteria:

• Histologically confirmed soft tissue sarcoma or mesothelioma.
• Ineligible for other high priority national or institutional study.
• Non-pregnant, non-lactating.
• Recurrent or progressive disease defined as an increase in size of any existing tumor mass, or the development of new tumor mass or masses, which is not amenable to definitive surgical therapy.
• Measurable disease defined as lesions that can be measured in at least one dimension by physical examination or by means of medical imaging techniques. Ascites and pleural effusions will not be considered measurable disease.
• Prior chemotherapy is allowed with the exception of prior treatment with Temozolomide or Azacitidine. Patients must have received prior 1st line therapy. There is no upper limit to the number of prior therapies received. Prior treatment with an alkylating agent is acceptable.
• Prior radiation therapy is allowed.
• At least 4 weeks since prior chemotherapy or at least 6 weeks since prior radiation therapy.
• Patients may have had another cancer but there must be convincing clinical evidence that the sarcoma is the disease requiring therapeutic intervention. (i.e. Several sarcoma patients have had had a prior cancer [Hodgkin's disease or breast cancer] treated years previously and then developed a clinically active sarcoma.)
• Clinical parameters: Life expectancy > 3 months, Age > 18 years, Performance Karnofsky performance status of greater than or equal to 60%.

• Required initial laboratory data:

  • Absolute neutrophil count > 1,500/mm3
  • Hemoglobin > 10.0 g/dl
  • Platelet count > 100,000/mm3
  • Total Bilirubin < 1.5 times upper limit of normal (ULN) for the laboratory.
  • Transaminases: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels must be < 2 x ULN. If there is known hepatic metastasis, transaminases may be < 5 times upper limit of normal.
  • Serum creatinine levels < 1.5 x ULN.
  • Women of child-bearing potential must have a negative serum pregnancy test prior to initiation of treatment.
• Men and women of child-bearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter (approximately 3 months).
• Capable of providing written, informed consent. Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks and discomforts.
• No serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g. serious infection).
• No uncontrolled central nervous system metastases.

Exclusion Criteria:

• Known or suspected hypersensitivity to azacitidine or mannitol
• Pregnant or breast-feeding
• Histology other than soft-tissue sarcoma or mesothelioma
• Active or uncontrolled infection or other serious systemic disease
• Prior treatment with temozolomide or azacitidine
• Pregnant or lactating women
• Uncontrolled central nervous system metastases
• Liver metastases
• Patients will not be excluded if they do not wish to participate in the second biopsy for tissue evaluation
• Subjects who have not had prior chemotherapy.