US-based Sunesis Pharmaceuticals has started an investigator-sponsored Phase I/II trial of vosaroxin in combination with azacitidine for the treatment of patients with myelodysplastic syndrome (MDS).
The open label, dose-escalation Phase I/II study is being carried out at the Washington University School of Medicine under the supervision of Meagan Jacoby instructor of Medicine, Division of Oncology.
About 40 patients with MDS who may have received up to three prior cycles of hypomethylating agent-based therapy will be enrolled in the trial.
In the trial, patients will be administered with vosaroxin (days one and four) and azacitidine (days one through seven) for a maximum of six cycles.
A total of six patients per cohort will be enrolled in the trial in order to assess the maximum tolerated dose (MTD) and dose limiting toxicity of the combination.
Other endpoints of the trial include best response, safety, tolerability, and event-free, progression-free, disease-free and overall survival.
The company said that about 20 additional patients will be enrolled, treated and evaluated at that dose level once the MTD is determined.
Jacoby said that additional therapeutic options are needed for patients with MDS.
"While azacitidine has been shown to improve survival in patients with high-risk MDS, existing therapies do not produce a remission in the majority of patients and are not curative," Jacoby added.
"Given its clinical profile, we believe that investigation of vosaroxin's activity in high-risk MDS is warranted."
Vosaroxin, a first-in-class anti-cancer quinolone derivative (AQD), both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis.
Sunesis executive vice president of development and chief medical officer Adam Craig said with the start of the trial, vosaroxin is now being studied in three investigator-sponsored trials at leading US medical research centers.
"We recently highlighted encouraging data in difficult-to-treat AML and high-risk MDS patients from a study at the MD Anderson Cancer Center and now look forward to learning more about the use of vosoraxin in MDS in this new study," Craig added.
"Overall, the results of our IST studies will provide us with valuable clinical data and a greater understanding of vosaroxin's potential as a new treatment option in MDS, as our pivotal Phase 3 VALOR trial in acute myeloid leukemia reaches completion in 2014."
The company also announced that it has been informed that the Cardiff University-sponsored LI-1 trial's Data Monitoring and Ethics Committee (DMEC) will recommend discontinuing the combination arm of vosaroxin and low dose cytarabine (LoDAC).
Cardiff University head of Haematology Alan Burnett is responsible for conducting the LI-1 trial.
Both the US Food and Drug Administration (FDA) and European Commission have previously granted orphan drug status to vosaroxin for the treatment of acute myeloid leukemia (AML).
In addition, vosaroxin has secured FDA fast track status for the potential treatment of relapsed or refractory AML in combination with cytarabine.