Phase II Study of Zometa (Zoledronic Acid) to Prevent Osteoporosis in Patients With Brain Tumors
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.
- 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
- 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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
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
James J. Vredenburgh, MD
United States: Federal Government
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