Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: everolimus; sunitinib
Intervention description: Everolimus was administered orally at 10 mg/day. Everolimus is formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.; Sunitinib was administered orally 50 mg daily, on a schedule of 4 weeks on/2 weeks off. Sunitinib was supplied as hard gelatin capsules of 12.5 mg, 25 mg, or 50 mg strength according to local practice.
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: 471.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RAD001; everolimus; sunitinib; renal cell carcinoma; kidney cancer; metastatic renal cell cancer; advanced kidney cancer

Summary:

      This study assessed the efficacy and safety of first-line RAD001 followed by second-line
      sunitinib versus the opposite sequence: first-line sunitinib followed by second-line RAD001
      for the treatment of patients with MRCC.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with advanced renal cell carcinoma.

          2. Patients with at least one measurable lesion.

          3. Patients with a Karnofsky Performance Status ≥70%.

          4. Adequate bone marrow function.

          5. Adequate liver function.

          6. Adequate renal function.

          7. Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)

          8. Women of childbearing potential must have had a negative serum pregnancy test within
             14 days prior to the administration of the study medication. Adequate contraception
             must be used while on study.

        Exclusion Criteria:

          1. Less than 4 weeks post-major surgery

          2. Patients who had radiation therapy within 4 weeks prior to start of study treatment
             (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study
             treatment start).

          3. Patients in need for major surgical procedure during the course of the study

          4. Patients with a serious non-healing wound, ulcer, or bone fracture

          5. Patients with a history of seizure(s) not controlled with standard medical therapy

          6. Patients who have received prior systemic treatment for their metastatic RCC

          7. Patients who have previously received systemic mTOR inhibitors (sirolimus,
             temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy,
             vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.

          8. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins
             (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity
             to RAD001 (everolimus) or other rapamycins or to its excipients

          9. Patients with a known hypersensitivity to sunitinib or its excipients

         10. History or clinical evidence of central nervous system (CNS) metastases. Note:
             Subjects who have previously-treated CNS metastases (surgery plus or minus
             radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria
             are eligible:

               -  Are asymptomatic and,

               -  have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment
                  and,

               -  have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)

         11. Clinically significant gastrointestinal abnormalities including, but not limited to:

               -  Malabsorption syndrome

               -  Major resection of the stomach or small bowel that could affect the absorption of
                  study drug

               -  Active peptic ulcer disease

               -  Inflammatory bowel disease

               -  Ulcerative colitis, or other gastrointestinal conditions with increased risk of
                  perforation

               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal
                  abscess within 28 days prior to beginning study treatment.

         12. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥160mmHg
             or diastolic blood pressure (DBP) of ≥ 95mmHg]

         13. Patients receiving chronic systemic treatment with corticosteroids or another
             immunosuppressive agent

         14. Patients with a known history of HIV seropositivity.

         15. Patients with active bleeding.

         16. Patients who have any severe and/or uncontrolled medical conditions or other
             conditions within the past 12 months that could affect their participation in the
             study such as:

               -  Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral
                  vascular disease, symptomatic congestive heart failure (NYHA II, III, IV),
                  myocardial infarction ≤ 6 months prior to first study treatment, serious
                  uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before
                  study treatment start.

               -  Prolongation of corrected QT interval (QTc) > 500 milliseconds (msecs).

               -  Severally impaired lung function as defined as spirometry and DLCO that is 50% of
                  the normal predicted value and/or 0^2 saturation that is 88% or less at rest on
                  room air.

               -  Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN.

               -  Any active (acute or chronic) or uncontrolled infection/disorders that impair the
                  ability to evaluate the patient or for the patient to complete the study.

               -  Liver disease such as chronic active hepatitis or chronic persistent hepatitis.

         17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).

         18. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the
             past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic
             anti-coagulating agents for at least 6 weeks are eligible.

         19. Patients who have a history of another primary malignancy and off treatment for ≤ 3
             years

         20. Female patients of child-bearing potential who are not using adequate birth control
             methods, or who are pregnant or breast feeding.

         21. Patients who are using other investigational agents or who had received
             investigational drugs ≤ 2 weeks prior to study treatment start.

         22. Patients unwilling or unable to comply with the protocol.