A Study of SB939 in Patients With Translocation-Associated Recurrent/Metastatic Sarcomas

Objectives:

• - To determine the efficacy of SB939 in translocation associated sarcoma patients.
• - To determine response duration, stable disease rate and progression free survival.
• - To evaluate toxicity of SB939.
• - To investigate potential molecular factors predictive of response.

60mg SB939 will be given every other day 3 times a week for 3 weeks followed by a week off. Patients may receive a maximum of 12 cycles if they have a response to treatment in the absence of disease progression or unacceptable toxicity. Patients with stable disease may continue therapy for a maximum of 6 cycles.

Inclusion criteria

• Patients with histologically diagnosed sarcomas that are associated with chromosomal translocation producing a fusion transcription factor oncogene.
• Patients must have measurable disease.
• A tissue block from primary or metastatic tumor must be available for confirmation of diagnosis, translocation subtype and correlative studies.
• Up to 1 prior chemotherapy regimen in the metastatic setting is permitted providing 28 days have elapsed.
• Prior radiation permitted provided a minimum of 28 days have elapsed.
• Surgery permitted provided at least 3 weeks have elapsed.
• Prior hormone therapy permitted.
• Patients must have life expectancy ≥ 12 weeks.
• Metastatic or locally recurrent disease incurable with standard treatment.
• Acceptable end-organ function. ECOG 0, 1 or 2.
• granulocytes ≥1.5x10/9/L
• platelets ≥100x10/9/L
• bilirubin ≤UNL
• potassium ≤UNL
• calcium, magnesium within normal limits
• AST, ALT ≤2.5 x UNL
• serum creatinine ≤UNL or creatinine clearance ≥50mL/min
• QTc ≤450m sec
• LVEF ≥50%
• Troponin I or T ≤ UNL

Exclusion criteria

• Cardiac exclusions; Patients with any preexisting uncontrolled cardiac condition.
• History of myocardial infarction at any time in the past.
• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 5 years.
• Patients with documented CNS metastases, unless adequately treated with radiation at least 30 days prior to enrollment. Patients cannot have concurrent anti-convulsants or dexamethasone for control of symptoms. Patients with leptomeningeal disease, even with treatment, cannot be enrolled due to generally poor prognosis.
• Inability to take oral medication. Patients must be able to swallow SB939 capsules and have no gastrointestinal abnormalities (e.g. bowel obstruction or previous gastric resection) which would lead to inadequate absorption of SB939.
• Previous treatment with an HDAC inhibitor.
• Treatment with another investigational therapy or other anticancer therapy within 28 days prior to study entry.
• Known HIV, hepatitis B or hepatitis C infections.
• Dysrhythmic drugs - use of agents with a known risk of Torsades De Pointe is not permitted during the study. A comprehensive list can be found at http://torsades.org.
• Presence of any chronic medical condition or comorbidity such as pulmonary disease, active CNS disease, active infection, psychiatric condition, or laboratory abnormality that may increase the risks associated with study participation/study drug administration or may interfere with the interpretation of study results.
• Women or men who are not sterile unless they use an adequate method of birth control. Female patients that are post-menopausal for at least 12 months or are surgically sterile are considered sterile.