Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma
Condition: Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Everolimus; Sunitinib
Intervention description: 10 mg by mouth once a day.; 50 mg by mouth daily for 4 weeks on / 2 weeks off
Intervention MeSH terms: Everolimus; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced non-clear cell renal cell cancer (RCC); Clear-cell renal cell carcinoma; Collecting duct carcinoma; Translocation carcinoma; Chromophobe; Everolimus; Sunitinib; Afinitor; RAD001; Sunitinib Malate; SUO11248; Sutent; ESPN

Summary:

      The goal of this clinical research study is to compare the effectiveness of Afinitor
      (everolimus) and Sutent (sunitinib) for the treatment of advanced renal cell carcinoma
      (kidney cancer). The safety of each treatment will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have advanced non-clear cell RCC, which may include but is not limited
             to the following subtypes: papillary I or II, chromophobe, collecting duct carcinoma
             (CDC), translocation or unclassified. Patients with conventional-type renal cell
             carcinoma who have >/= 20% sarcomatoid component in their primary tumor are eligible.
             Patients who have sarcomatoid features in FNA or core biopsy of any metastatic site
             are eligible, if they have an underlying renal cell carcinoma primary tumor.

          2. Patients must have at least one measurable site of disease that has not been
             previously irradiated. If the patient has had previous radiation to the marker
             lesion(s), there must be evidence of progression since the radiation

          3. ECOG performance status 0-1

          4. Age >/= 18 years

          5. Patients must have adequate organ and marrow function within 14 days prior to study
             entry as defined below: a) Hemoglobin >/= 9 g/dl (tx allowed); b) absolute neutrophil
             count >/=1,500/microL; c) platelets >/= 100,000/microL; d) total bilirubin </= 1.5
             mg/dl; e) AST(SGOT) or ALT (SGPT) </=2.5 X institutional uln, except in known hepatic
             metastasis, wherein may be </= 5 x ULN; f) Serum Creatinine </= 1.5 x ULN (as long as
             patient does not require dialysis)

          6. INR and PTT </= 1.5 x ULN within 14 days prior to study entry. Therapeutic
             anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of
             warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of
             randomization.

          7. Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides
             </= 2.5 x ULN within 14 days prior to study entry.

          8. Female patients of childbearing potential (not postmenopausal for at least 12 months
             and not surgically sterile) must have a negative serum or urine pregnancy test within
             14 days before study entry. Pregnancy test must be repeated if performed > 14 days
             before starting study drug.

          9. Patients must give written informed consent prior to study entry, in keeping with the
             policies of each institution.

         10. Patients with a history of major psychiatric illness must be judged (by the treating
             physician) able to fully understand the investigational nature of the study and the
             risks associated with the therapy.

         11. Patients with controlled brain metastases are allowed on protocol if they had solitary
             brain metastases that was surgically resected or treated with radiosurgery or Gamma
             knife, without recurrence or edema for 3 months (90days).

        Exclusion Criteria:

          1. No other malignancies within the past 2 years except for adequately treated carcinoma
             of the cervix or basal (without recurrence post-surgery or post-radiotherapy) or
             squamous cell carcinomas of the skin.

          2. No prior systemic therapy for RCC including prior adjuvant therapy or investigational
             drug is allowed.

          3. Patients currently receiving anticancer therapies or who have received anticancer
             therapies within 4 weeks (28 days) from enrollment into this study (including
             chemotherapy and targeted therapy) are excluded. However, patients are permitted to
             receive bisphosphonates. Also, patients who completed palliative radiation therapy
             prior to enrollment in this trial are eligible.

          4. Patients, who have had a major surgery or significant traumatic injury (injury
             requiring > 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study
             drug, patients who have not recovered from the side effects of any major surgery
             (defined as requiring general anesthesia) or patients that may require major surgery
             during the course of the study.

          5. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450
             enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) or
             CYP3A4 inhibitors is not recommended on this study.

          6. Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as: a) Symptomatic
             congestive heart failure of New York heart Association Class III or IV; b) unstable
             angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6
             months of start of study drug, serious uncontrolled cardiac arrhythmia or any other
             clinically significant cardiac disease; c) severely impaired lung function as defined
             as 02 saturation that is 88% or less at rest on room air

          7. (#6 cont'd) d) uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN;
             e) active (acute or chronic) or uncontrolled severe infections requiring antibiotic
             intervention; f) liver disease such as cirrhosis, chronic active hepatitis or chronic
             persistent hepatitis

          8. Patients must not have history of other diseases, metabolic dysfunction, physical
             examination finding, or clinical laboratory finding giving reasonable suspicion of a
             disease or condition that contraindicates the use of sunitinib or everolimus or that
             might affect the interpretation of the results of the study or render the subject at
             high risk from treatment complications.

          9. Concomitant treatment with drugs with dysrhythmic potential (terfenadine, quinidine,
             procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and
             indapamide) is not recommended.

         10. Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

         11. Patients should not receive immunization with attenuated live vaccines within one week
             (7 days) of study entry or during study period.

         12. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases.

         13. A known history of HIV sero-positivity.

         14. Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of everolimus and/or sunitinib (e.g., ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
             bowel resection).

         15. Patients with an active, bleeding diathesis.

         16. Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods. If barrier contraceptives
             are being used, these must be continued throughout the trial by both sexes. Hormonal
             contraceptives are not acceptable as a sole method of contraception. (Women of
             childbearing potential must have a negative urine or serum pregnancy test within 7
             days prior to study entry. Pregnancy test must be repeated if performed > 7 days
             before administration of everolimus and sunitinib)