Conditions: Soft Tissue Sarcoma Mesothelioma
Keywords: Soft Tissue Sarcoma Mesothelioma Azacitidine Temozolomide Temodar
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 27
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine safety and toxicity for the combination of Temozolomide and Azacitidine in the treatment of Advanced Soft Tissue Sarcoma or Malignant Mesothelioma. This is a single-center, open-label, single-arm Phase I dose-escalation trial. Patients will be evaluated with complete history and physical as well as laboratory studies (complete blood count, metabolic panel, liver function tests), biopsy, and imaging of all sites of measurable disease. This study will be conducted over the course of 3 years.

Detailed description:
The primary objective of the study is to determine the clinical and laboratory toxicities as well as acceptability/tolerance of this dose schedule of combined drug treatment with temozolomide and azacitidine.

Secondary objectives include determination of biochemical response to azacitidine as defined as change in methylation status. The investigators will specifically be looking at changes in genome wide methylation patterns as determined by two high-throughput platforms:

1. A single nucleotide polymorphism chip-based method (MSNP) for genome wide epigenetic profiling
2. CpG island promoter arrays will be performed to focus on promoter methylation status.

The investigators will also monitor clinical response, time to progression and overall survival.

Arms:
arm 1: Subjects will receive azacitidine in combination with temozolomide

Interventions: intervention 1: Azacitidine intervention 2: Temozolomide
Intervention descriptions: intervention 1: Azacitidine will be delivered sub-cutaneously for 5 days intervention 2: Temozolomide will be given starting on day 8 for 5 days at a dose of 200 mg/m2 po qd x 5 days

Protocol document: