Zoledronate in Preventing Osteoporosis in Patients With Primary Malignant Glioma

Osteoporosis Clinical Trial

Official title:

Phase II Study of Zometa (Zoledronic Acid) to Prevent Osteoporosis in Patients With Brain Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00301873
• Other study ID #: Pro00010125
• Secondary ID: P50NS020023
• Status: Completed
• Phase: Phase 2
• First received: March 9, 2006
• Last updated: February 13, 2013
• Start date: May 2006
• Est. completion date: September 2012

Study information

• Verified date: February 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Zoledronate may prevent bone loss in patients with primary malignant glioma.

PURPOSE: This phase II trial is studying how well zoledronate works in preventing osteoporosis in patients with primary malignant glioma.

Description:

This is an open-labeled trial to determine the incidence of osteoporosis in brain tumor patients and effect of Zometa every three months. Zometa will be given at 4 mg intravenously over 15 minutes every 3 months for 1 year. The patients will undergo a baseline bone densitometry test that will be repeated at six months and one year. Information on the patient's tolerability of Zometa as well as any skeletal-related complications that happen will be collected. Data with respect to the dose and duration of glucocorticoids and anticonvulsants will be collected since both of these therapies have shown to directly affect bone density. Serial markers (N-telopeptide) of bone turn over will be collected at baseline and every 3 months prior to the infusion of Zometa. Karnofsky performance status will be monitored as a function of mobility.

Accrual Goal 60 patients over a 18-month period, averaging 3-4 new enrollees per month. Thirty-five patients to reach the 6-month assessment.

OBJECTIVES:

• To determine the bone mineral density of the patients at baseline and any changes over 12 months while receiving Zometa every 3 months.

• To determine the incidence of skeletal-related complications in this cohort of brain tumor patients.

• To determine the safety and tolerability of Zometa in brain tumor patients.

• To determine the effects of glucocorticoids and anticonvulsants on bone density.

Response Criteria The primary efficacy endpoint will be the patient's bone densitometry, and how it changes over the course of one year of Zometa therapy. The bone densitometry after 6 months and 12 months of Zometa will be compared to the baseline. The secondary efficacy variable will be the prevention of skeletal-related events (compression fracture, any fracture requiring surgery) which given the heterogeneity of the patient population will be a qualitative variable. Date with respect to the dose and duration of glucocorticoids and anticonvulsants will be collected since both of these therapies have shown to directly affect bone density. Serial markers (N-telopeptide) of bone turn over will be collected.

Outcome assessment The patient's bone densitometry will be determined by Dexa-scan at the baseline, after six months of Zometa and after one year of Zometa. The bone density (Dexa- scan) will be reviewed by the outside radiologist or Duke radiology in conjunction with the primary investigator. A decrease of > -0.5 on the T-score will be coded as a treatment failure and patients will be discontinued from the study and referred to Endocrinology or Orthopedic Surgery for best clinical management. In addition, any skeletal-related event (fractures) will be coded as a treatment failure. The patient population will be heterogeneous in terms of their functional capacity, exercise capacity, anticonvulsant and glucocorticoid dos

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have histologically confirmed diagnosis of a primary brain tumor.

2. Patients must be on Depakote ( Valproic Acid) or one of the following enzyme inducing anticonvulsants (EIAC) therapies. Phenobarbital, Dilantin, Trileptal, Tegretol and/or on more than physiologic replacement steroid therapy (Dexamethasone >0.75 mg/d, prednisone >5 mg/d or hydrocortisone >20 mg/d).

3. Age > 18 years.

4. Karnofsky performance score > 60%

5. Adequate renal and liver function as demonstrated by laboratory values performed within 14 days, inclusive, prior to the administration of Zometa, except for the creatinine, which will be within 72 hs of Zometa administration:

• Serum creatinine < 2.0 mg/dl and calculated creatinine clearance of >60 mL/min

• Total serum bilirubin < 1.5 times upper limit of laboratory normal

• Serum glutamoc-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) < 2.5 times upper limit of laboratory normal

• Alkaline phosphatase of <2 times upper limit of laboratory normal

6. Patients must have recovered from any effects of major surgery.

7. Patients must have a life expectancy of greater than 12 weeks.

8. Patients or legal guardian must give written, informed consent.

Exclusion Criteria:

1. Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics.

2. Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.

3. Known HIV positivity or AIDS-related illness.

4. Pregnant or nursing women.

5. Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 72hours prior to administration of study and be practicing medically approved contraceptive precautions.

6. Men who are not advised to use and effective method of contraception.

7. Patients previously diagnosed with osteoporosis requiring oral bisphosphonates.

8. Known hypersensitivity to Zometa® (zoledronic acid) or other bisphosphonates

9. Current active dental problems including infection of the teeth or jawbone osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.

10. Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants).

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors
• Central Nervous System(CNS)Malignancies
• Osteoporosis

Intervention

Drug:
• IV Zometa
Zometa will be given at 4 mg intravenously over 15 minutes every 3 months for 1 year.

Locations

Country	Name	City	State
United States	Duke Comprehensive Cancer Center	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	National Institute of Neurological Disorders and Stroke (NINDS), Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Patients With Change in Combined Bone Mass Density T-score <= -0.5.	Percent of patients who failed treatment as defined by a decrease of 0.5 or more from baseline in the combined T-score as measured by Dexa-scan. The patient's bone densitometry was determined by Dexa-scan at baseline, after 6 months of Zometa and after 1 year of Zometa. The t-score, which is a comparison of a person's bone density with that of a healthy 30-year-old of the same sex, was generated by Dexa-scan for the spine and femur. The combined T-score is the minimum of the T-score for the spine and femur. A lower t-score implies a lower BMD.	6 and 12 months	No
Secondary	Skeletal-related Complications	Number of patients who experience skeletal-related complications during the administration of Zoledronate.	1 year	Yes
Secondary	Mean Change in Bone Mass Density (BMD)	Mean change in the combined t-score was measured by Dexa-scan. The patients bone density was determined by Dexa-scan at baseline, after 6 months Zometa and after 12 months of Zometa. The t-score, which is a comparison of a person's bone density with that of a healthy 30-year old of the same sex, was generated by Dexa-scan for the spine and femur. A lower t-score implies a lower BMD. The combined t-score is the minimum of the t-score for the spine and that for the femur. BMD change from baseline at 6 and 12 months in the combined t-score was defined as the follow-up combined t-score minus the baseline combined t-score.	6 & 12 months	No