Official Title: “Bone-Targeted Therapy Combining Zoledronate With Atorvastatin in Renal Cell Carcinoma: A Phase II Study”

Primary Objective:

1. Evaluate clinical outcome based on the time to skeletal events after bone-targeted therapy.

Secondary Objectives:

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2008

Kidney cancer often spreads (metastases) to the bones. Zoledronate is designed to protect the bones from pain and from breaking as a result of cancer. Atorvastatin is a drug that lowers cholesterol levels in the blood. Combining these medications may make zoledronate more effective.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a physical exam and routine urine tests. You will have x-rays, computerized tomography (CT) scans, and a bone scan to check on the status of the disease.

Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will be given zoledronate intravenously (IV--through a needle in your vein) over fifteen minutes,1 time every 4 weeks.

You will take a pill, atorvastatin, by mouth once time a day every day that you are on the study. Every 4 weeks is considered 1 study "cycle".

You will need to return to M. D. Anderson for check-ups every 8 -12 weeks. Urine will be collected for routine tests. You will have x-rays, bone scans, and/or CT scans to check on the status of the disease.

You will receive at least 2 cycles of treatment unless intolerable side effects occur or your disease gets worse. You may receive more than 2 cycles if you are benefitting from the study drugs.

You will be followed every 8 weeks for up to 1 year for skeletal events (symptoms related to disease moving to or getting worse in your bones). You will be taken off study if you experience a skeletal event or at the end of the 1-year monitoring period. Monitoring may be done with a local doctor or at M. D. Anderson. No extra testing or procedures are needed during this period.

This is an investigational study. The combination of the 2 drugs given in this study is investigational for the treatment of bone metastases. Zoledronate is approved for the treatment of bone metastases. Atorvastatin has been approved by the FDA for lowering cholesterol. About 38 patients will take part in this study. All will be enrolled at M. D.

Anderson.

Intervention(s) in this Clinical Trial

• Drug: Zoledronate
  • 4 mg IV Once Every 4 Weeks
• Drug: Atorvastatin
  • 20 mg PO Daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Zoledronate + Atorvastatin

Primary Measures

• To find out if combining zoledronate (Zometa) and Lipitor (atorvastatin) will help kidney cancer patients whose cancer has spread to their bones by delaying bone-related problems (like pain or fractures).
  • Time Frame: 2 Years
    Safety Issue?: No

Inclusion Criteria:

• Histologically confirmed renal cell carcinoma
• Must have evidence of predominant bone metastases on X-rays, bone scan, MRI or CT scan. No requirement for bidimensionally measurable lesions.
• Impending complications (such as pathological fractures and spinal cord compressions) from skeletal metastases must be controlled by surgery or radiation therapy.
• Patients with prior or on concurrent immunotherapy or chemotherapy are eligible, excluding those on drugs that will interact with statins (Cytochrome P450 2C9
• Pathway).
• Patients with prior or concurrent treatment with bisphosphonates or statins are eligible.
• Patients with hypercalcemia are eligible.
• 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.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study.

Exclusion Criteria:

• Patients of childbearing potential not practicing adequate contraception.
• Patients with poor dentition or recent major dental procedures.
• 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.
• Overt psychosis or mental disability or otherwise incompetent to give informed consent.
• Known hypersensitivity to Zometa (zoledronic acid), other bisphosphonates, or to fluvastatin.
• 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.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g., extraction, implants)
• Active liver disease or unexplained persistent elevation of ALT or AST > 2 times ULN
• Serum creatine kinase (CK) > 3 times ULN
• 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.
• History of alcohol abuse as such condition independently predisposes patients to myopathy.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Shi-Ming Tu, MD Principal Investigator U.T.M.D. Anderson Cancer Center  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00490698

Study ID Number: 2005-0652

ClinicalTrials.gov Identifier: NCT00490698

Health Authority: United States: Institutional Review Board