A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Cabozantinib tablets; Everolimus (Afinitor) tablets
Intervention MeSH terms: Everolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 658.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: renal cell cancer; kidney; vascular endothelial growth factor receptor 2 (VEGFR2); tyrosine kinase inhibitor; hepatocyte growth factor receptor protein (MET); von Hippel-Lindau gene

Summary:

      The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with
      Everolimus (Afinitor) on progression-free survival (PFS) and overall survival (OS) in
      subjects with advanced renal cell cancer that has progressed after prior VEGFR tyrosine
      kinase inhibitor therapy.
    

Eligibility criteria:

        Select Inclusion Criteria:

          1. Documented histological or cytological diagnosis of renal cell cancer with a
             clear-cell component.

          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 platelet
             inhibitors.

          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.