Zoledronate With Atorvastatin in Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00490698
• Other study ID #: 2005-0652
• Status: Completed
• Phase: Phase 2
• First received: June 21, 2007
• Last updated: February 13, 2013
• Start date: October 2006
• Est. completion date: January 2012

Study information

• Verified date: February 2013
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms
• Renal Cell Carcinoma

Intervention

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

Locations

Country	Name	City	State
United States	UT MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

Manoukian GE, Tannir NM, Jonasch E, Qiao W, Haygood TM, Tu SM. Pilot trial of bone-targeted therapy combining zoledronate with fluvastatin or atorvastatin for patients with metastatic renal cell carcinoma. Clin Genitourin Cancer. 2011 Dec;9(2):81-8. doi: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Time to First Skeletal-related Event	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	No

External Links

•   The University of Texas (UT) MD Anderson Cancer Center official website