A Study of RO4929097 in Patients With Advanced Renal Cell Carcinoma That Have Failed Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Therapy

Inclusion Criteria

• Patients must have histologically or cytologically confirmed predominant clear cell, renal cell carcinoma, NOS, that is recurrent or metastatic
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; scans must be completed within 4 weeks prior to starting study treatment
• Patients must have had one prior therapy for non-resectable renal cell carcinoma with a VEGF/VEGFR targeted therapy (e.g. sunitinib, sorafenib, other VEGFR tyrosine kinase inhibitor, or bevacizumab)
• Prior treatment with mTOR inhibitors (Everolimus, Temsirolimus, or rapamycin) for non-resectable disease is permitted
• Prior immunotherapy is permitted
• Only one line of prior VEGF/VEGFR is permitted
• Life expectancy of greater than 3 months
• ECOG performance status = = 60%)
• Patients must have normal organ and marrow function as defined below (within 7days prior to starting study treatment):
• Hemoglobin >= 90 g/L
• Absolute granulocyte count >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Total bilirubin = = mL/min/1.73 m^2 for patients with creatinine levels above institutional (using Cockcroft-Gault formula)
• Patients must have no serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, psychiatric illness, or any other medical conditions that might be aggravated by treatment or limit compliance
• Patients must have no active malignancy at any other site
• Patients must be able to take oral medication and have no evidence of bowel obstruction
• The effects of RO4929097 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Notch signal pathway inhibitors are known to be teratogenic, if women of childbearing potential do not abstain from sexual activity (documentation that they have been abstinent from sexual activity at least 4 weeks prior to study entry) they must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry; women of childbearing potential be can either be abstinent or use two forms of contraception for the duration of study participation, and be either abstinent or use two forms of contraception for at least 12 months post-treatment; men must use condoms when sexually active with women for the duration of study participation and at least 12 months post-treatment
• Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately
• Pregnancy Testing; women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of RO4929097 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of RO4929097; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing RO4929097, the investigator or clinical staff must confirm and document the patient's use of two contraceptive methods or abstinence, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of RO4929097
• Female patients of childbearing potential are defined as follows:
• Patients with regular menses
• Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive m