Clinical trial NCT00915694: Nelfinavir Mesylate, Radiation Therapy, and Temozolomide in Treating Patients With Glioblastoma Multiforme
Official title: A Phase I Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-06-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose of nelfinavir mesylate
timeFrame: 90 days
measure: Dose-limiting toxicities as assessed by NCI CTC v3.0
timeFrame: 90 days
Secondary outcomes:
measure: Progression-free survival
timeFrame: One year
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Jay F. Dorsey, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: