Neoadjuvant Clinical Trial to Evaluate the Efficacy of Bevacizumab for Renal Cell Carcinoma
Condition: Renal Cell Carcinoma; Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Bevacizumab
Intervention description: 10 mg/kg IV on day 1 of each 14-day cycle.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; Kidney Cancer; Bevacizumab; Avastin; RCC

Summary:

      The goal of this clinical research study is to learn if bevacizumab (Avastin®) can control
      metastatic renal cell carcinoma (RCC). The safety of the treatment will also be studied.

      Objectives:

      Primary:

        1. To assess the efficacy of neoadjuvant therapy of bevacizumab by evaluating time to
           progression.

        2. Toxicities of therapy with bevacizumab in RCC.

      Secondary:

      Clinical:

        1. Response rate

        2. Duration of response

        3. Overall Survival

      Preclinical:

        1. Serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and MMP-2, Interleukin 6
           (IL-6), vascular endothelial growth factor (VEGF), and Basic Fibroblast Growth Factor
           (bFGF) pre- and post- therapy (optional studies).

        2. Tissue expression of Phospho-epidermal growth factor receptor (EGFR), VEGF, vessel count
           CD31/34, AKT and Phospho-AKT, mitogen-activated protein kinase (MAPK), transforming
           growth factor-alpha (TGF-alpha), phospho-STAT3 and TUNEL post therapy (optional
           studies).

        3. complementary DNA (cDNA) microarray analysis of tissue post-therapy (optional studies).

        4. Tissue expression of tumor infiltrating lymphocytes and tumor antigens

        5. Pathological response rate in primary tumor.

        6. To evaluate the Single Nucleotide Polymorphisms (SNP) patterns in nephrectomy specimens
           from patients participating in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically or cytologically confirmed clear cell metastatic RCC who
             are eligible for cytoreductive nephrectomy.

          -  Patients must have measurable disease, defined as a lesion that can be accurately
             measured in at least one dimension (longest diameter to be recorded) and measures
             greater than or equal to 20 mm with conventional techniques or greater than or equal
             to 10 mm with spiral computed tomography (CT) scan. This does not include primary
             tumors, which will be removed.

          -  The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             1

          -  Female patients of childbearing potential (i.e. premenopausal, no hysterectomy) must
             have a normal plasma beta human chorionic gonadotropin (bHCG) within 24 hours prior to
             enrolling in the study due to the possible teratogenic effect. Patients with an
             elevated bHCG will undergo appropriate evaluation to rule out pregnancy (i.e. referral
             to Gyn service, pelvic ultrasound) and if pregnancy is ruled out and elevated bHCG is
             determined to be of tumor origin, patients will be permitted to proceed on study.

          -  Patients of child fathering or childbearing potential must agree to practice a form of
             medically acceptable birth control while on study, i.e. condoms.

          -  Patients must give written informed consent prior to initiation of therapy, in keeping
             with the policies of the institution. Patients with a history of major psychiatric
             illness must be judged able to fully understand the investigational nature of the
             study and the risks associated with the therapy. The only approved consent is attached
             to this protocol.

          -  Patients must have ability to comply with study and/or follow-up procedures.

          -  Patients must have adequate organ and marrow function within 14 days as defined below:
             absolute neutrophil count >/=1,500/micro platelets >/= 75,000/micro Hgb > 9.0 g/dL
             (may be transfused or receive epoetin alfa permitted) total bilirubin </= 2.0 mg/dL
             albumin > 3.0 g/dL serum creatinine </= 2.0 mg/dL aspartate aminotransferase (AST or
             SGOT) and/or alanine aminotransferase (ALT or SGPT) </= 2.5 * upper limit of normal
             (ULN), no liver metastases AST(SGOT) and/or ALT (SGPT) </= 5 * ULN, liver metastases
             present.

        Exclusion Criteria:

          -  Patients must not have organ allografts.

          -  Patients must not have had major surgical procedure, open biopsy, or significant
             traumatic injury within 28 days prior to Day 0, or anticipation of need for major
             surgical procedure during the course of the study (other than defined by protocol); or
             fine needle aspirations or core biopsies within 7 days prior to Day 0.

          -  No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma
             of any site, or other cancers for which the patient has been adequately treated and
             disease free for 5 years.

          -  Patients must not have received any systemic anticancer therapy. Radiation therapy is
             allowed if >/= 2 weeks from study drug administration.

          -  Patients must not be scheduled to receive another experimental drug while on this
             study. Patients are permitted to be on concomitant bisphosphonates and megestrol
             acetate.

          -  Patients must not have a primary brain tumor (excluding meningiomas other benign
             lesions), any brain metastases, leptomeningeal disease, seizure disorders not
             controlled with standard medical therapy, or history of stroke within the past 5
             years.

          -  History of serious systemic disease, including myocardial infarction or unstable
             angina within the last 12 months, history of hypertensive crisis or hypertensive
             encephalopathy, uncontrolled hypertension (blood pressure of >140/90 mmHg on
             medication), New York Heart Association (NYHA) Grade II or greater congestive heart
             failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic
             atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular
             tachycardia are eligible), significant vascular disease or symptomatic peripheral
             vascular disease.

          -  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 an investigational drug or that
             might affect the interpretation of the results of the study or render the subject at
             high risk from treatment complications.

          -  Patients receiving any concomitant systemic therapy for renal cell cancer are
             excluded, but patients taking bisphosphonates and megestrol acetate are not excluded.

          -  Patients must not require total parenteral nutrition with lipids.

          -  Patients must not have significant proteinuria at baseline. Patients who are
             unexpectedly discovered to have greater than or equal to 1+ proteinuria on routine
             urinalysis at baseline should undergo a 24 hour urine collection, which must be an
             adequate collection and must demonstrate less than or equal to 1g of protein/24 hour
             to allow participation in the study.

          -  Patients must not have clinical history of coagulopathy, bleeding diathesis or
             thrombosis.

          -  Patients must not have a serious, nonhealing wound, ulcer, or bone fracture.

          -  Pregnancy (positive pregnancy test) or lactation.

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment.

          -  Know hypersensitivity to any component of bevacizumab.