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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.
 
ClinicalTrials.gov Identifier: NCT00694837
Recruitment Status : Completed
First Posted : June 11, 2008
Last Update Posted : April 10, 2015
Sponsor:
Collaborator:
Maastricht University Medical Center
Information provided by (Responsible Party):
Maastricht Radiation Oncology

Tracking Information
First Submitted Date  ICMJE June 9, 2008
First Posted Date  ICMJE June 11, 2008
Last Update Posted Date April 10, 2015
Study Start Date  ICMJE March 2009
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2008)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2008)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma
Official Title  ICMJE Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
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.

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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: B
Intervention: Drug: nelfinavir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2008)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00694837
Other Study ID Numbers  ICMJE 07-09-04/07
EudraCT number 2008-001078-34
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maastricht Radiation Oncology
Study Sponsor  ICMJE Maastricht Radiation Oncology
Collaborators  ICMJE Maastricht University Medical Center
Investigators  ICMJE
Principal Investigator: Brigitta Baumert, MD PhD Maastricht Radiation Oncology
PRS Account Maastricht Radiation Oncology
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP