Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma
Condition: Renal Cell Carcinoma; Renal Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Everolimus
Intervention description: Tablet form taken orally once a day
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: everolimus

Summary:

      The purpose of this study is to determine if certain features of tumor specimens sampled
      prior to therapy can predict for the likelihood of responding to everolimus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have at least one site of disease which in the opinion of the
             investigator is safely accessible by CT guided biopsy or metastasectomy. Safely
             accessible metastatic disease will be defined to include those lesions which are
             palpable with no overlying viscera and are at least 2cm in size. Given the paucity of
             subcutaneous lesions in RCC, lesions which are felt to be safe to biopsy will also be
             allowed. These lesions include pleural-based tumors, peripheral liver lesions, kidney
             lesions and bone lesions with exophytic soft tissue component. As with palpable
             lesions, these other lesions should be at least 2cm in size with no overlying viscera.

          -  At least one measurable site of disease, other than the biopsy site, according to
             RECIST criterial that has not been previously irradiated. Th the patient has had
             previous radiation to the marker lesion(s), there must be evidence of progression
             since the radiation

          -  Metastatic renal carcinoma with histologic confirmation by the treating center of
             either primary or a metastatic lesion. Non-clear cell histologies will be allowed

          -  18 years of age or older

          -  Minimum of four weeks since any major surgery, completion of radiation, or completion
             of all prior systemic anticancer therapy (adequately recovered from the acute
             toxicities of any prior therapy)

          -  ECOG Performance status of 1 or less

          -  Adequate bone marrow, liver and renal function as outlined in the protocol

          -  Fasting serum cholesterol < 300mg/dL OR < 7.75 mmol/L AND fasting triglycerides < 2.5
             x ULN

          -  Life expectancy of greater than 6 months

        Exclusion Criteria:

          -  Prior treatment with any investigation drug within the preceding 4 weeks

          -  Chronic treatment with systemic steroids or another immunosuppressive agent

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases. Treated brain
             metastases will be allowed. Treated brain metastases are defined as having no evidence
             of progression or hemorrhage after treatment and no ongoing requirement for
             dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT)
             during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for
             brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma
             Knife, LINAC or equivalent) or a combination as deemed appropriate by the treating
             physician. Patients with CNS metastases treated by neurosurgical resection performed
             within 3 months prio to day 1 will be excluded.

          -  Other malignancies within the past 3 years except for adequately treated carcinoma of
             the cervix or basal or squamous cell carcinomas of the skin

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study

          -  Uncontrolled diabetes mellitus as defined by a fasting serum > 1.5 x ULN

          -  A known history of HIV seropositivity.

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of everolimus

          -  Patients with active, bleeding diathesis or on systemic anticoagulation. Aspirin is
             permitted.

          -  Women who are pregnant or breast feeding, or women/men able to conceive and unwilling
             to practice an effective method of birth control.

          -  Patients who have received prior treatment with an mTOR inhibitor.

          -  Patients with known hypersensitivity to everolimus or other rapamycins or to its
             excipients.

          -  History of noncompliance to medical regimens