A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy
1. Documented histological or cytological diagnosis of renal cell cancer with a
2. Measurable disease as determined by the investigator.
3. Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib,
axitinib, pazopanib or tivozanib).
4. Recovery from toxicities related to any prior treatments, unless AE(s) are clinically
nonsignificant and/or stable on supportive therapy.
5. Adequate organ and marrow function.
6. Sexually active fertile subjects(male and female)must agree to use medically accepted
methods of contraception during the course of the study and for 4 months after the
last dose of study treatment.
7. Female subjects of childbearing potential must not be pregnant at screening.
Select Exclusion Criteria:
1. Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT
inhibitor (eg, temsirolimus), or cabozantinib.
2. Receipt of any type of small molecule kinase inhibitor (including investigational
kinase inhibitor) within 2 weeks before randomization.
3. Receipt of any type of anticancer antibody (including investigational antibody)
within 4 weeks before randomization.
4. Radiation therapy for bone metastasis within 2 weeks, any other external radiation
therapy within 4 weeks before randomization. Systemic treatment with radionuclides
within 6 weeks before randomization. Subjects with clinically relevant ongoing
complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery and stable for at least 3 months before randomization.
6. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or
7. Chronic treatment with corticosteroids or other immunosuppressive agents.
8. Serious illness other than cancer.
9. Major surgery within 3 months before randomization. Complete wound healing from
major surgery must have occurred 1 month before randomization and from minor surgery
at least 10 days before randomization.
10. Pregnant or lactating females.
11. Diagnosis of another malignancy within 2 years before randomization, except for
superficial skin cancers, or localized, low grade tumors.