Velcade and Sorafenib in Unresected or Metastatic Renal Cell Carcinoma
Condition: Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Velcade and Sorafenib
Intervention description: Velcade will be administered intravenously; sorafenib will be self-administered on an outpatient basis. At least 2 courses will be administered to each patient unless there is early progression of disease or unacceptable toxicity. Repeated courses may be given to patients who benefit from the treatment (complete or partial remission or stabilization of disease)
Intervention MeSH terms: Bortezomib; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; metastatic renal cell cancer; kidney cancer

Summary:

      This is an open label, non-randomized, single arm phase II study. The primary objective of
      this study is to investigate the efficacy of combination of sorafenib and VELCADE®
      (bortezomib). The primary efficacy endpoint is Progression-Free Survival (PFS). The secondary
      objectives of this study are to:

      Assess the response rate of this combination in this patient population and Assess the
      toxicity of this combination in this patient population
    

Eligibility criteria:

        Inclusion Criteria:

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study.

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

          -  All patients, 18 years or older with cytologically confirmed clear cell renal with no
             prior chemotherapy are eligible.

          -  Patients must have a life expectancy of at least 12 weeks

          -  Patients must have a Zebroid performance of 0-2

          -  Patients should have adequate bone marrow function defined by an absolute peripheral
             granulocyte count of > 1500 cells/mm3 and platelet count > 100,000/mm3 and absence of
             a regular red blood cell transfusion requirement.

          -  Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and
             Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase
             (SGPT) < two times the upper limit of normal, and adequate renal function as defined
             by a Serum creatinine < 1.5 x the upper limit of normal.

        Exclusion Criteria:

        Patients meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Patients with non-measurable disease.

          -  Patients who are unable to take medications orally.

          -  Patients with resectable renal cell carcinoma

          -  Patients with a history of Hepatitis B, or Hepatitis C

          -  Patients known to be Human Immunodeficiency Virus (HIV) positive

          -  Patients with poorly controlled diabetes mellitus

          -  Patients with poorly controlled hypertension or hypotension

          -  Chronic pulmonary disease and a diffusion capacity < 50 %, or a forced vital capacity
             (FVC) or forced expiratory volume in 1 second (FEV1) of <50%

          -  Severe renal impairment (Creatinine clearance [CrCL]< 13 ml/min)

          -  Patients with known malabsorption syndromes.

          -  Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at Screening has to be documented by the investigator as not medically
             relevant.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol or sorafenib.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum B-human chorionic gonadotropin
             (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
             required for post-menopausal or surgically sterilized women.

          -  Patient has received other investigational drugs with 28 days before enrollment.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          -  Patients may receive no other concurrent chemotherapy or radiation therapy (XRT)
             during this trial.

          -  Patients may not have received XRT within 4 weeks prior to the first treatment.