Capecitabine, Gemcitabine, and Bevacizumab in Combination for Patients With Sarcomatoid Renal Cell Carcinoma
Condition: Renal Cell Carcinoma; Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Capecitabine; Gemcitabine; Bevacizumab
Intervention description: 800 mg/m^2 By Mouth Twice Daily On Days 1-21.; 900 mg/m^2 By Vein Over 30 Minutes on Days 1 and 15.; 10 mg/kg By Vein On Days 1 and 15.
Intervention MeSH terms: Bevacizumab; Gemcitabine; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Healthy volunteers: No
Keywords: Genitourinary; Kidney Cancer; Sarcomatoid Renal Cell Carcinoma; Renal Cell Carcinoma; RCC; Sarcomatoid Carcinoma of the Kidney; Unresectable renal cell carcinoma; Capecitabine; Xeloda; Gemcitabine; Gemzar; Bevacizumab; Anti-VEGF monoclonal antibody; rhuMAb-VEGF; Avastin; Vascular Endothelial Growth Factor; VEGF

Summary:

      The goal of this clinical research study is to learn if the combination of 3 drugs
      (gemcitabine, capecitabine, and bevacizumab) can help to control metastatic or unresectable
      renal cell carcinoma. The safety of this drug combination will also be tested.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically demonstrated, metastatic or unresectable sarcomatoid carcinoma of the
             kidney, defined as the following: • A tumor biopsy (primary or metastasis) must show
             at least one focus of RCC (one of the recognized types); and, • A tumor biopsy
             (primary or metastasis) must have at least 10% of the sample showing sarcomatoid
             histology.

          2. (# 1 cont'd) • Patients with primary tumor in place are eligible if there is any
             percentage of sarcomatoid dedifferentiation on a needle biopsy (primary or
             metastasis), and the radiographic appearance of the primary tumor on CT scan is
             typical of RCC. For these patients, due to the small tumor sample, it is not required
             to identify an area of typical RCC histology as long as the morphologic and
             immunostaining characteristics are consistent with RCC.

          3. At least one site of measurable disease (may include primary tumor).

          4. No prior cytotoxic chemotherapy. Any prior immunotherapy is permitted.

          5. No prior bevacizumab treatment. Prior sorafenib or sunitinib is permitted.

          6. Zubrod performance status 2 or better

          7. Adequate organ and bone marrow function: • Absolute Neutrophil Count (ANC) >/= 1,500 •
             Platelets >/=100,000 • Total bilirubin </= 1.5 mg/dl • AST and ALT </= 3x upper limit
             normal • Creatinine clearance > 50 cc/min (measured or calculated by Cockcroft
             formula: Creatinine Clearance = [(140 - age) x wt (kg)]/[72 x creat (mg/dl)], for
             females x 0.85. Patients with creatinine clearance of 30-50 ml/min are eligible with
             an initial dose-reduction of capecitabine to the (-1) dose level.

          8. Female patients of childbearing potential (last menses < 2 years) must have a negative
             blood pregnancy test within 7 days prior to starting treatment.

          9. All patients must agree to practice adequate contraception if sexually active for the
             duration of the trial and for 2 months after discontinuation of the study drugs

         10. Written informed consent.

        Exclusion Criteria:

          1. Patients with history of myocardial infarction, transient ischemic attack (TIA),
             stroke, pulmonary embolism, or history of deep vein thrombosis within the preceding 12
             months.

          2. Patients with major risk of bleeding, such as active brain metastases. Patients with
             controlled or small brain metastases will be eligible based on clinical assessment of
             the actual bleeding risk.

          3. Patients with history of any major surgical procedure within the preceding 28 days.

          4. Patients with baseline blood pressure >/= 140 systolic or >/= 90 diastolic.

          5. Patients with nephrotic syndrome (proteinuria > 2 grams per 24 hours)

          6. History of other malignancy, unless it is clinically non-threatening (such as
             non-melanoma skin cancer) or controlled for 2 years prior to study entry.

          7. Prior treatment with gemcitabine, capecitabine, or any fluoropyrimidine.

          8. Prior unanticipated severe reaction to fluoropyrimidine therapy or known
             hypersensitivity to 5-FU.

          9. Any concurrent chemotherapy or radiotherapy.

         10. Lack of physical integrity of the upper gastrointestinal tract, inability to swallow
             tablets or those who have malabsorption syndrome.

         11. Clinically significant cardiac disease not well controlled with medication, such as
             symptomatic coronary artery disease, congestive heart failure, and cardiac
             arrhythmias.

         12. Serious concurrent infections or other serious medical conditions, including
             uncontrolled diabetes.

         13. Any serious non-healing wound, ulcer, or active bone fracture.

         14. Any concurrent coumadin therapy. Patients who were previously on coumadin maintenance
             may switch to aspirin or low-molecular-weight heparin.

         15. Patients who have had an organ allograft.

         16. Unwillingness to give written informed consent.