rdea119 and sorafenib combination dose escalation study

Conditions: Advanced Cancer

Summary: phase 1/2 dose escalation study to investigate the combination of rdea119 and sorafenib in advanced cancer patients.


Eligibility criteria:
inclusion criteria: - eastern cooperative oncology group (ecog) performance status of 0-1. - histological or cytological confirmed diagnosis of a solid tumor. in the dose escalation phase, the tumor must be unresectable and locally advanced, or metastatic, and either no proven effective therapy exists or the patient cannot tolerate such therapy. patients enrolled in the expanded mtd phase of the study must have either hcc or another select tumor type (melanoma, head and neck, colorectal, breast, or thyroid). for hcc patients in the expanded mtd phase: - documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable. histological confirmation is mandatory for patients without cirrhosis. - patients with cirrhosis may have a clinical diagnosis of hcc by the american association for the study of liver diseases (aasld) criteria.-cytotoxic chemotherapy; a targeted agent, including sorafenib; or other experimental treatment) are eligible. for non-hcc patients in the expanded mtd phase: - the tumor must be amenable to biopsy and the patient must be willing to consent to biopsy. - life expectancy of \> 3 months. - evidence of measurable disease by recist criteria on computer assisted tomography (ct) or magnetic resonance imaging (mri). - normal/adequate swallowing capability, functional small bowel intact, and no malabsorption problems (in order to maximally quantify pk absorption characteristics). - amylase and lipase \ or equal to 8.5 g/l. - anc \> or equal to 1,500/mm3. - platelet count \> or equal to 75,000/mm3. - total bilirubin \ 3 years prior to study entry. - swallowing dysfunction and/or malabsorption syndrome that would impair sorafenib and rdea119 treatment. - cardiac disease: congestive heart failure \> new york heart association (nyha) class 2. patients must not have unstable angina or new onset angina (within the last 3 months) or myocardial infarction (mi) within the past 6 months. - cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. - uncontrolled hypertension - known human immunodeficiency virus (hiv) infection. - 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, as well as the concurrent treatment with any of the agents listed in section 3.7 of the protocol. these and other medications that are inhibitors and inducers of cyp3a4 and cyp2c19 should be discussed with the sponsor. - patients with known hypersensitivity to any of the drugs or components given in this protocol. - 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. - evidence of uncontrolled active infections except hcv and hbv. - other serious medical or psychiatric illness that would not permit the patient to be managed according to the protocol.