Zoledronate With Atorvastatin in Renal Cell Carcinoma
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
Drug: Atorvastatin
20 mg PO Daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Median Time to First Skeletal-related Event [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.
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2005-0652
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: October 1, 2006 to January 31, 2008. All recruitment done at UT MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Zoledronate + Atorvastatin |
|---|---|
| Arm/Group Description | Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily |
| Period Title: Overall Study | |
| STARTED | 11 |
| COMPLETED | 1 |
| NOT COMPLETED | 10 |
Baseline Characteristics
| Arm/Group Title | Zoledronate + Atorvastatin |
|---|---|
| Arm/Group Description | Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily |
| Overall Participants | 11 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
56.6
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
11
100%
|
| Region of Enrollment (participants) [Number] | |
| United States |
11
100%
|
Outcome Measures
| Title | Median Time to First Skeletal-related Event |
|---|---|
| Description | 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. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Four participants did not experience skeletal events. |
| Arm/Group Title | Zoledronate + Atorvastatin |
|---|---|
| Arm/Group Description | Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily |
| Measure Participants | 7 |
| Median (95% Confidence Interval) [months] |
9
|
Adverse Events
| Time Frame | 4 years and 3 months | |
|---|---|---|
| Adverse Event Reporting Description | "Definitely" and "Probably" related World Health Organization (WHO)classification grade 1 and 2 adverse events were reported. | |
| Arm/Group Title | Zoledronate + Atorvastatin | |
| Arm/Group Description | Zoledronate 4 mg intravenous (IV) once every 4 Weeks + Atorvastatin 20 mg orally (PO) daily | |
All Cause Mortality |
||
| Zoledronate + Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Zoledronate + Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/11 (18.2%) | |
| Blood and lymphatic system disorders | ||
| Transient ischemic attack | 1/11 (9.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Bone Pain | 1/11 (9.1%) | |
Other (Not Including Serious) Adverse Events |
||
| Zoledronate + Atorvastatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 11/11 (100%) | |
| Blood and lymphatic system disorders | ||
| Lymphopenia | 1/11 (9.1%) | |
| General disorders | ||
| Fatigue | 11/11 (100%) | |
| Infections and infestations | ||
| Fever | 1/11 (9.1%) | |
| Skin and subcutaneous tissue disorders | ||
| Desquamatory rash | 1/11 (9.1%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Shi-Ming Tu, MD / Professor |
|---|---|
| Organization | The University of Texas (UT) MD Anderson Cancer Center |
| Phone | |
| CR_Study_Registration@mdanderson.org |
- 2005-0652