Zoledronate With Atorvastatin in Renal Cell Carcinoma

Condition(s) targeted: Kidney Cancer; Renal Cell Carcinoma

Intervention: Zoledronate (Drug); Atorvastatin (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Shi-Ming Tu, MD, Principal Investigator, Affiliation: U.T.M.D. Anderson Cancer Center

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.

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

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

Primary outcome: 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).

Detailed description: 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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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 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.

U.T.M.D. Anderson Cancer Center, Houston, Texas 77030, United States

Starting date: October 2006
Last updated: June 9, 2008