A phase II study of SB939, a novel pan-histone deacetylase inhibitor, in patients with translocation-associated recurrent/metastatic sarcomas—NCIC-CTG IND 200

摘要: ABSTRACT Fusion transcription genes/oncoproteins generated from translocation-associated sarcomas modulate gene via histone deacetylase-containing chromatin modifying complexes. This phase II study of SB939 in this subgroup sarcoma demonstrated a 3-month progression-free rate 49%. Exploratory analysis showed that these with HDAC score ≥5 may derive more clinical benefit. Background A is characterized by defining chromosomal translocations, creating fusion factor oncogenes. Resultant oncoproteins associate chromatin-modifying complexes containing deacetylases (HDAC), and lead to epigenetic transcriptional dysregulation. inhibitors were shown be effective vitro, reversing repression complexes, restoring PTEN expression apoptosis the PI3K/Akt/mTOR pathway. Patients methods an oral inhibitor classes 1 2 HDAC. Eligible patients recurrent or metastatic (TAS) local pathology treated 60 mg/day every other day for 3 4 weeks. Central review was conducted oncogenes characterized, HDAC2 correlated efficacy pre-specified methods. Results Twenty-two median cycles. Fourteen assessable response confirmed specific translocations; 8 had best stable disease (SD) (median duration 5.4 months) no objective responses. The survival (PFS) Among those ≥5, 7/10 SD, versus 0/3 Conclusion stopped prematurely due prolonged unavailability SB939. No responses seen. Although observed SD high interesting, small sample size, definitive conclusion can drawn about patient population. Clinical trial NCT01112384.