A Phase I Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of nelfinavir mesylate when given concurrently
with radiotherapy and temozolomide followed by temozolomide alone in patients with
glioblastoma multiforme.
- Determine the safety and dose-limiting toxicities of this regimen in these patients.
Secondary
- Determine the progression-free survival (PFS) and overall survival (OS) of patients
treated with this regimen.
- Compare the observed median values of PFS and OS obtained in this study to the
historical median values of 6.9 months and 14.6 months, respectively.
OUTLINE: This is a dose-escalation study of nelfinavir mesylate.
Patients receive oral nelfinavir mesylate twice daily beginning 7-10 days before the
initiation of chemoradiotherapy and continuing until the completion of chemoradiotherapy.
Patients undergo radiotherapy once daily 5 days a week and receive concurrent oral
temozolomide once daily for 6 weeks. Beginning 4 weeks after completion of nelfinavir
mesylate and chemoradiotherapy, patients receive oral temozolomide alone once daily on days
1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed WHO grade IV supratentorial astrocytoma (glioblastoma
multiforme)
- Newly diagnosed disease
- Has undergone maximal surgical resection
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Serum creatinine < 1.5 times upper limit of normal (ULN)
- AST or ALT < 2 times ULN
- Serum bilirubin < 1.5 mg/dL
- No known HIV infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior cranial radiotherapy
- More than 30 days since prior investigational agents
- No other concurrent investigational agents
- No concurrent use of any of the following drugs:
- Antiarrhythmics (i.e., amiodarone or quinidine)
- Antimycobacterials (i.e., rifampin)
- Ergot derivatives (i.e., dihydroergotamine, ergonovine, ergotamine, or
methylergonovine)
- Herbal products (i.e., St. John's wort)
- HMG-CoA reductase inhibitors (i.e., lovastatin or simvastatin)
- Neuroleptics (i.e., pimozide)
- Sedatives and/or hypnotics (i.e., midazolam or triazolam)
- Concurrent corticosteroids allowed provided dose has been stable or decreasing for ≥
14 days prior to study entry
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of nelfinavir mesylate
Safety Issue:
Yes
Principal Investigator
Jay F. Dorsey, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
Unspecified
Study ID:
CDR0000644278
NCT ID:
NCT00915694
Start Date:
April 2009
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult giant cell glioblastoma
- adult gliosarcoma
- adult glioblastoma
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
