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

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

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.

Study Overview

• Status: Terminated
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Drug: temozolomide; Procedure: adjuvant therapy; Drug: nelfinavir mesylate

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose of nelfinavir mesylate	90 days
Dose-limiting toxicities as assessed by NCI CTC v3.0	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	5 years
Progression-free survival	One year

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jay F. Dorsey, MD, PhD, Abramson Cancer Center of the University of Pennsylvania

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 5, 2009
• First Submitted That Met QC Criteria: June 5, 2009
• First Posted (Estimate): June 8, 2009

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 22, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Protease Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Temozolomide; Nelfinavir
• Other Study ID Numbers: CDR0000644278; UPCC-01309; IRB#809463