Zoledronate With Atorvastatin in Renal Cell Carcinoma

February 13, 2013 updated by: M.D. Anderson Cancer Center

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

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

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Zoledronate + Atorvastatin
Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily
4 mg IV Once Every 4 Weeks
Other Names:
  • Zometa
20 mg PO Daily
Other Names:
  • Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Time to First Skeletal-related Event
Time Frame: Up to 1 year
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). Time to skeletal events monitored every 8 weeks for at least 1 year.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Shi-Ming Tu, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

January 1, 2012

Study Registration Dates

First Submitted

June 21, 2007

First Submitted That Met QC Criteria

June 22, 2007

First Posted (ESTIMATE)

June 25, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

March 18, 2013

Last Update Submitted That Met QC Criteria

February 13, 2013

Last Verified

February 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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