Phase 1/2 dose escalation study to investigate the combination of RDEA119 and sorafenib in advanced cancer patients

Inclusion Criteria:

• ECOG performance status of 0-1.
• Histological or cytological confirmed diagnosis of a solid tumor which is unresectable and locally advanced, or metastatic in which no proven effective therapy exists or for patients who are intolerant to such therapy.
• Patients > 18 years of age.
• Life expectancy of > 3 months
• Evidence of measurable disease by RECIST criteria.
• No clinically significant abnormalities in Amylase and Lipase, Hemoglobin, ANC, Platelet count, Total Bilirubin, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT), PTT, prothrombin time (PT), and INR or Creatinine.
• Patients receiving anti-coagulation treatment with an agent such as warfarin or low molecular weight heparin may be allowed to participate, but must not have active bleeding or a pathologic condition that carries a high risk of bleeding.
• Patients must not be pregnant or breast-feeding. Men and women of reproductive potential may not participate in this study unless they have agreed to use an effective contraceptive method while on study.
• Patients must be within normal range cardiac function as measured by echocardiogram or multiple-gated acquisition (MUGA) scan.

Exclusion Criteria:

• Previous treatment with sorafenib that required a dose reduction due to toxicity or previous treatment with RDEA119.
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Swallowing dysfunction and/or malabsorption syndrome
• Concurrent use of chemotherapy not indicated in the study protocol or any other investigational agents < 4 weeks from the first dose of study drug.
• Cardiac disease or Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Known HIV infection or other uncontrolled active infections.
• Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Evidence or history of bleeding diathesis or coagulopathy.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug.
• The use of inhibitors or inducers of CYP3A4 and CYP2C19 enzymes.
• Patients with abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or small bowel resection, any of which is within 6 months of study entry.
• Patients with abdominal radiation resulting in chronic diarrhea.
• Patients with documented central nervous system (CNS) metastasis who are not off steroids and other CNS therapies.
• Other serious medical or psychiatric illness that would not permit the patient to be managed according to the protocol.