Zoledronate With Atorvastatin in Renal Cell Carcinoma - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00490698

Purpose

Objectives:

Primary:

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

Secondary:

Evaluate clinical outcome based on the presence of calcification at the site of osteolytic metastases
Measure bone-formation and resorption markers at baseline and during bone-targeted therapy.
Assess effect of the bone-targeted regimen on serum cholesterol levels

Condition	Intervention	Phase
Kidney Cancer Renal Cell Carcinoma	Drug: Zoledronate Drug: Atorvastatin	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Bone-Targeted Therapy Combining Zoledronate With Atorvastatin in Renal Cell Carcinoma: A Phase II Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer

Drug Information available for: Zoledronic acid Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Median Time to First Skeletal-related Event [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Efficacy assessed using Simon 2-stage optimal design, based on primary endpoint (ie, time to skeletal event) at 6 months after bone-targeted therapy. Efficacy of the treatment regimen was assessed by time to skeletal events, defined as a metastatic site requiring radiotherapy or any surgical intervention (eg, embolization, radiofrequency ablation, intrathecal catheter placement) or complications from skeletal metastatic lesions (eg, pathologic fracture, spinal cord compression).

Enrollment:	11
Study Start Date:	October 2006
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Zoledronate + Atorvastatin Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily	Drug: Zoledronate 4 mg IV Once Every 4 Weeks Other Name: Zometa Drug: Atorvastatin 20 mg PO Daily Other Name: Lipitor

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.

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 </= 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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times upper limits of normal (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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00490698

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Shi-Ming Tu, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00490698 History of Changes
Other Study ID Numbers:	2005-0652
Study First Received:	June 21, 2007
Last Updated:	January 26, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Kidney Cancer
Renal Cell Carcinoma
Bone-Targeted Therapy
Zoledronate

Zometa
Atorvastatin
Lipitor
RCC

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Atorvastatin

Zoledronic acid
Diphosphonates
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012