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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00915694
• Other study ID #: CDR0000644278
• Secondary ID: UPCC-01309IRB#80
• Status: Terminated
• Phase: Phase 1
• Start date: April 2009
• Est. completion date: December 2015

Study information

• Verified date: April 2019
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: December 2015
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• nelfinavir mesylate

• temozolomide

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Abramson Cancer Center of the University of Pennsylvania	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of nelfinavir mesylate		90 days
Primary	Dose-limiting toxicities as assessed by NCI CTC v3.0		90 days
Secondary	Progression-free survival		One year
Secondary	Overall survival		5 years

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database