Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma
Condition: Advanced Non-clear Cell Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Everolimus; Sunitinib
Intervention description: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.; 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Intervention MeSH terms: Everolimus; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cancer; kidney cancer; sutent; everolimus; renal cancer; papillary renal cell; chromophobe renal cell; papillary; chromophobe

Summary:

      To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic
      renal cell carcinoma (mRCC) with non-clear cell pathology.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell
             pathology.

          2. RCC tumor tissue available for correlative sciences, from either primary or metastatic
             site or both.

          3. At the time of screening, at least 4 weeks since prior palliative radiation therapy
             and/or major surgery, and resolution of all toxic effects of prior therapy to National
             Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version
             4.0) Grade 1.

          4. Subject must have radiographic evidence of metastatic disease with at least 1
             measurable per RECIST 1.1 criteria (Attachment 1)].

          5. Age > 18 years.

          6. Adequate laboratory values

          7. Karnofsky Performance Status ≥ 60 (Attachment 2).

          8. Life expectancy of at least 3 months.

          9. Written, signed, dated, and witnessed Institutional Review Board (IRB) or
             Institutional Ethics Committee (IEC) approved informed consent form (ICF) before any
             screening procedures are performed.

        Exclusion Criteria:

          1. Subjects with a history of or active central nervous system (CNS) metastases.

          2. Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy,
             chemotherapy, biologic or experimental therapy.

          3. Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type
             pathology.

          4. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.

          5. Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the
             screening visit.

          6. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or
             radiation therapy.

          7. Presence of a non-healing wound or ulcer.

          8. Grade 3 hemorrhage within the past month.

          9. Hypertension with systolic blood pressure of >180 mm Hg and/or diastolic pressure >100
             mm Hg.

         10. Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history
             of congestive heart failure with an ejection fraction <50%, or history of unstable
             angina, myocardial infarction, coronary artery bypass graft, cerebrovascular accident,
             transient ischemic attack, or pulmonary embolism within 6 months of entry.

         11. Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) > 10% despite therapy.

         12. A history of interstitial pneumonitis.

         13. Subjects with active autoimmune disorder(s) being treated with immunosuppressive
             agents within 4 weeks prior to the screening visit.

         14. Subjects receiving immunosuppressive agents and those with chronic
             viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV).

         15. Patients who have receive immunization with attenuated live vaccines within one week
             of study entry or during study period.

         16. Patients with active infection(s), active antimicrobial therapy or serious
             intercurrent illness.

         17. History of other prior malignancy in past 5 years.

         18. Pregnant or nursing women.

         19. Major medical/psychiatric illness that, in the investigator's judgment, will
             substantially increase the risk associated with the subject's participation in this
             study, including inability to absorb oral medications and history of noncompliance to
             medical regimens.

         20. Known hypersensitivity to any of the components in everolimus or sunitinib product

         21. Subjects taking agents that significantly prolong the QTc interval are not eligible.

         22. Proteinuria with a spot urine protein/creatinine ratio >2 or 24 hour urine protein >2
             grams per 24 hours.

         23. Severely impaired lung function as defined as spirometry and Carbon Monoxide Diffusing
             Capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is
             88% or less at rest on room air.

         24. Advanced liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh
             class C).