Nelfinavir Mesylate, Radiation Therapy, and Temozolomide in Treating Patients With Glioblastoma Multiforme

Abramson Cancer Center at Penn Medicine

Status and phase

Terminated

Phase 1

Conditions

Brain and Central Nervous System Tumors

Treatments

Procedure: adjuvant therapy

Radiation: radiation therapy

Drug: nelfinavir mesylate

Drug: temozolomide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00915694

IRB#809463

UPCC-01309

CDR0000644278

Details and patient eligibility

About

RATIONALE: Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir mesylate together with radiation therapy and temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir mesylate when given together with radiation therapy and temozolomide in treating patients with glioblastoma multiforme.

Full description

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.

Enrollment

15 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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