Zoledronate With Atorvastatin in Renal Cell Carcinoma
Condition: Kidney Cancer; Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Zoledronate; Atorvastatin
Intervention description: 4 mg IV Once Every 4 Weeks; 20 mg PO Daily
Intervention MeSH terms: Zoledronic Acid; Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Healthy volunteers: No
Keywords: Kidney Cancer; Renal Cell Carcinoma; Bone-Targeted Therapy; Zoledronate; Zometa; Atorvastatin; Lipitor; RCC

Summary:

      Objectives:

      Primary:

      Evaluate clinical outcome based on the time to skeletal events after bone-targeted therapy

      Secondary:

        1. Evaluate clinical outcome based on the presence of calcification at the site of
           osteolytic metastases

        2. Measure bone-formation and resorption markers at baseline and during bone-targeted
           therapy.

        3. Assess effect of the bone-targeted regimen on serum cholesterol levels
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed renal cell carcinoma

          2. Must have evidence of predominant bone metastases on X-rays, bone scan, MRI or CT
             scan. No requirement for bidimensionally measurable lesions.

          3. Impending complications (such as pathological fractures and spinal cord compressions)
             from skeletal metastases must be controlled by surgery or radiation therapy.

          4. Patients with prior or on concurrent immunotherapy or chemotherapy are eligible,
             excluding those on drugs that will interact with statins (Cytochrome P450 2C9
             Pathway).

          5. Patients with prior or concurrent treatment with bisphosphonates or statins are
             eligible.

          6. Patients with hypercalcemia are eligible.

          7. Adequate physiologic reserves as evidenced by:Zubrod performance status of </= 2;
             Transaminase and conjugated bilirubin less than twice the upper limit of normal;
             Creatinine Clearance >/= 30 ml/min.

          8. Patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study.

        Exclusion Criteria:

          1. Patients of childbearing potential not practicing adequate contraception.

          2. Patients with poor dentition or recent major dental procedures.

          3. History of other malignancies other than non-melanoma skin cancer or carcinoma-in-situ
             of the cervix unless in complete remission and off therapy for that disease for at
             least 5 years.

          4. Overt psychosis or mental disability or otherwise incompetent to give informed
             consent.

          5. Known hypersensitivity to Zometa (zoledronic acid), other bisphosphonates, or to
             fluvastatin.

          6. Current active dental problems including infection of the teeth or jawbone (maxilla or
             mandibular); dental or fixture trauma, or a current or prior diagnosis of
             osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after
             dental procedures.

          7. Recent (within 6 weeks) or planned dental or jaw surgery (e.g., extraction, implants)

          8. Active liver disease or unexplained persistent elevation of alanine aminotransferase
             (ALT) or aspartate aminotransferase (AST) > 2 times upper limits of normal (ULN)

          9. Serum creatine kinase (CK) > 3 times ULN

         10. Patients taking concurrent agents that may increase risk of myopathy such as fibric
             acid derivatives, nicotinic acid, cyclosporine, azole antifungals (itraconazole,
             ketoconazole, and fluconazole), macrolide antibiotics (erythromycin, clarithromycin,
             HIV protease inhibitors, nefazodone, delavirdine, cyclosporine, and grapefruit juice.

         11. History of alcohol abuse as such condition independently predisposes patients to
             myopathy.