Phase II Study of Zometa (Zoledronic Acid) to Prevent Osteoporosis in Patients With Brain Tumors
18 Years
N/A
Both
Brain Tumors, Osteoporosis, Central Nervous System(CNS)Malignancies
Trial Information
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.
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
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).
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Percent of Patients With Change in Combined Bone Mass Density T-score <= -0.5.
Outcome Description:
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.
Outcome Time Frame:
6 and 12 months
Safety Issue:
No
Principal Investigator
James J. Vredenburgh, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Duke University
Authority:
United States: Federal Government
Study ID:
Pro00010125
NCT ID:
NCT00301873
Start Date:
May 2006
Completion Date:
September 2012
Related Keywords:
- Brain Tumors
- Osteoporosis
- Central Nervous System(CNS)Malignancies
- osteoporosis
- adult anaplastic astrocytoma
- adult giant cell glioblastoma
- adult anaplastic oligodendroglioma
- adult gliosarcoma
- adult mixed glioma
- recurrent adult brain tumor
- adult glioblastoma
- Brain Neoplasms
- Neoplasms
- Osteoporosis
- Glioma
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
