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

Sponsor

Abramson Cancer Center of the University of Pennsylvania (Other)

Overall Status

Terminated

CT.gov ID

NCT00915694

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: nelfinavir mesylate Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma

Actual Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm NFV-RT-Tem	Drug: nelfinavir mesylate Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy

Arm

Intervention/Treatment

Experimental: Single arm

NFV-RT-Tem

Drug: nelfinavir mesylate

Drug: temozolomide

Procedure: adjuvant therapy

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of nelfinavir mesylate [90 days]
Dose-limiting toxicities as assessed by NCI CTC v3.0 [90 days]

Secondary Outcome Measures

Progression-free survival [One year]
Overall survival [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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