Carfilzomib in Refractory Renal Cell Carcinoma (RCC)
Condition: Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Carfilzomib
Intervention description: 20 mg/m2 over 30 minutes by vein infusion on Days 1 and 2 and a dose of 56 mg/m2 over 30 minutes by vein infusion on Days 8, 9, 15, and 16 of each 4 week cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Cancer; Refractory Renal Cell Carcinoma; RCC; Clear cell kidney cancer with metastatic disease; Carfilzomib

Summary:

      The goal of this clinical research study is learn if carfilzomib can help control kidney
      cancer. The safety of this drug will also be studied.

      Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells
      cannot repair themselves, this may cause them to die.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Biopsy proven clear cell kidney cancer with metastatic disease. Progressive disease or
             intolerance to at least one but not more than three (3) prior systemic therapy(ies)

          2. Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >/= 20 mm with conventional
             techniques or as >/= 10 mm with spiral CT scan.

          3. Age >/= 18 years

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          5. Adequate hepatic function with serum ALT and AST </= 3.0 times the upper limit of
             normal and serum direct and total bilirubin </= 1.5 times the upper limit of normal.

          6. Absolute neutrophil count (ANC) >/= 1.0 × 10^9/L; patients with an ECOG performance
             status of 2 at study entry must have an ANC >/= 1.5 x 10^9/L

          7. Hemoglobin >/= 8 g/dL (80 g/L) within 14 days prior to beginning study treatment
             (subjects may be receiving red blood cell [RBC] transfusions in accordance with
             institutional guidelines); Patients with an ECOG performance status of 2 at study
             entry must have a hemoglobin >/= 9 g/dL (transfusion assistance acceptable)

          8. Platelet count >/= 50 × 10^9/L; Patients with an ECOG performance status of 2 at study
             entry must have a platelet count >/= 100 × 10^9/L

          9. Creatinine clearance (CrCl) >/= 30 mL/minute, either measured or calculated using a
             standard formula (eg, Cockcroft and Gault)

         10. Written informed consent in accordance with federal, local, and institutional
             guidelines.

         11. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and
             to practice contraception during the study and for a period of 6 weeks after you stop
             receiving the study drug

         12. Male subjects must agree to practice contraception during the study and for a period
             of 6 weeks after you stop receiving the study drug

        Exclusion Criteria:

          1. Brain metastases not controlled with surgery, whole brain radiotherapy, or with
             stereotactic radiosurgery

          2. Systemic therapy within two weeks of treatment initiation

          3. Pregnant or lactating females

          4. Major surgery within 21 days prior to beginning study treatment

          5. Acute active infection requiring treatment (systemic antibiotics, antivirals, or
             antifungals) within 14 days prior to beginning study treatment

          6. Known human immunodeficiency virus infection

          7. Active hepatitis B or C infection

          8. Unstable angina or myocardial infarction within 4 months prior to beginning study
             treatment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe
             coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus
             syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction
             system abnormalities unless subject has a pacemaker

          9. Uncontrolled hypertension (defined by BP consistently > 150/100) or uncontrolled
             diabetes (defined by HbA1c > 8.5) within 14 days prior to beginning study treatment

         10. Nonhematologic malignancy within the past 2 years with the exception of a) adequately
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or
             less with stable prostate-specific antigen levels; or d) cancer considered cured by
             surgical resection or unlikely to impact survival during the duration of the study,
             such as localized transitional cell carcinoma of the bladder or benign tumors of the
             adrenal or pancreas

         11. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
             beginning study treatment

         12. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             carfilzomib)

         13. Contraindication to any of the required concomitant drugs or supportive treatments,
             including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
             drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

         14. Subjects with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis within 14 days prior to beginning study treatment

         15. Any other clinically significant medical disease or condition that, in the
             Investigator's opinion, may interfere with protocol adherence or a subject's ability
             to give informed consent