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Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00694837
Recruitment Status : Completed
First Posted : June 11, 2008
Last Update Posted : April 10, 2015
Maastricht University Medical Center
Information provided by (Responsible Party):
Maastricht Radiation Oncology

Brief Summary:

The objectives of the trial are:

To assess safety, tolerability and activity of nelfinavir given neo-adjuvant and concomitant to chemoradiotherapy with temozolomide in patients with a newly diagnosed glioblastoma multiforme.

To describe the possible effect of nelfinavir on functional imaging To describe the activity of nelfinavir in vivo on blocking the AKT pathway.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: nelfinavir Phase 1

Detailed Description:
Glioblastoma multiforme is the most malignant and common, about 50%, variant of all primary brain tumours. The treatment strategies for this disease have not changed appreciably for many years consisting of a surgical intervention (biopsy or tumour resection) and post-operative local radiotherapy until several years ago. Combined chemoradiotherapy with temozolomide is at the moment the standard medical practice after results of the joint EORTC-NCIC phase III study randomizing between radiotherapy alone and combined chemoradiotherapy with temozolomide showed a significant improvement in 2-years survival from 8% to 24% for the combined treatment arm (Stupp 2005). Given the poor prognosis of these patients and the still poor treatment response, further therapeutic improvement will remain the most challenging topic for the future. The next step to further improve survival for this patient group would be the addition of biological modifying and/or antiangiogenic therapies. These strategies are motivated by the fact that glioblastomas often express very high levels of vascular endothelial growth factor which is a key mediator of blood vessel growth as high expression of EGFR, which upregulates the downstream PI3K-AKTpathway. (Fischer I, Carmeliet P, Koul D) One possible candidate is nelfinavir, a protease inhibitor interfering with Akt activity downstream of EGFR and upstream of VEGF. (Geng L, Gorski D, HLu B)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
Study Start Date : March 2009
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: B Drug: nelfinavir
The start dose of nelfinavir in phase 1 is 1000mg BID. The maximum administered dose, if no DLT occurs, will be1250 mg BID (2500mg). Nelfinavir will be administered 1 week before start of the chemoradiotherapy until the last day of chemoradiotherapy.

Primary Outcome Measures :
  1. Fase I: To determine the MTD of nelfinavir as an adjuvant in the radiochemotherapy treatment in primary glioblastoma patients. Fase 2: Progression free survival at 6 months [ Time Frame: Fase 1: after treatment; fase 2: 6 months after treatment ]

Secondary Outcome Measures :
  1. Fase 1/2: Incidence of acute toxicity; OS; Metabolic ratios of SUV of serial 18F-FDG: assessed by PET-CT.Fase 1:6-months PFS; Relative blood flow measurement by perfusion MRI. Fase 2: PFS at 12 months; Phosphorylation of AKT in tumour tissue. [ Time Frame: fase 1: 6 months after treatment; fase 2: 12 months after treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed glioblastoma multiforme at primary diagnosis
  • Tumours which do enhance on pre-operative imaging
  • Age >=18-65 years
  • WHO performance status 0-2, RTOG- RPA class III-IV.
  • No recent (< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
  • Patient able to tolerate full course of radiotherapy
  • No previous radiotherapy to the head and neck area.
  • Prior neurosurgery within 6 weeks of treatment
  • No previous irradiation of the brain.
  • No previous chemotherapy
  • No prior or concurrent medical condition which would make treatment difficult to complete. Medication with steroids is allowed.
  • No use of terfenadine, astemizol, cisapride, sildenafil, lovastatin or simvastatin and other concurrent medication that is metabolized by the CYP3A4 isoenzyme and cannot be replaced with other equivalent medications for the period of the study: antiarrhythmics (amiodarone, quinidine), neuroleptics (pimozide), sedative/hypnotic agents (midazolam, triazolam), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), HMG-CoA reductase inhibitors (atorvastatin), rifampin, rifabutin, felodipine, nifedipine, and sildenafil or St. John's wort.
  • Adequate haematological, renal and hepatic function
  • No uncontrolled infectious disease, absence of known HIV infection, chronic hepatitis B or hepatitis C infection
  • Absence of any medical condition, which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction)
  • All patients of reproductive potential (male and female) must use effective contraception for the whole duration of the treatment and until 6 months thereafter. Females must not be pregnant or lactating
  • Willing and able to comply with the study prescriptions
  • Written informed consent before patient registration

Exclusion Criteria:

The opposite from above

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00694837

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Maastricht Radiation Oncology
Maastricht, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht Radiation Oncology
Maastricht University Medical Center
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Principal Investigator: Brigitta Baumert, MD PhD Maastricht Radiation Oncology
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Responsible Party: Maastricht Radiation Oncology Identifier: NCT00694837    
Other Study ID Numbers: 07-09-04/07
EudraCT number 2008-001078-34
First Posted: June 11, 2008    Key Record Dates
Last Update Posted: April 10, 2015
Last Verified: April 2015
Keywords provided by Maastricht Radiation Oncology:
functional imaging
AKT pathway
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents