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Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma

This study has suspended participant recruitment.
Sponsor:
Collaborator:
Maastricht University Medical Center
Information provided by:
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00694837
First received: June 9, 2008
Last updated: January 24, 2013
Last verified: January 2013
History of Changes
  Purpose

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 Intervention Phase
Glioblastoma
 Drug: nelfinavir
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Maastricht Radiation Oncology:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 6
Study Start Date: March 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00694837

Locations
Netherlands
Maastricht Radiation Oncology
Maastricht, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht Radiation Oncology
Maastricht University Medical Center
Investigators
Principal Investigator: Brigitta Baumert, MD PhD Maastricht Radiation Oncology
  More Information

No publications provided

Responsible Party: Philippe Lambin, Prof. PhD., Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00694837     History of Changes
Other Study ID Numbers: 07-09-04/07, EudraCT number 2008-001078-34
Study First Received: June 9, 2008
Last Updated: January 24, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:
glioblastoma
nelfinavir
functional imaging
AKT pathway

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nelfinavir
 HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013