Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
18 Years
65 Years
Both
Glioblastoma
Trial Information
Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
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)
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Outcome Time Frame:
Fase 1: after treatment; fase 2: 6 months after treatment
Safety Issue:
Yes
Principal Investigator
Brigitta Baumert, MD PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Maastricht Radiation Oncology
Authority:
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study ID:
07-09-04/07
NCT ID:
NCT00694837
Start Date:
March 2009
Completion Date:
December 2013
Related Keywords:
- Glioblastoma
- glioblastoma
- nelfinavir
- functional imaging
- AKT pathway
- Glioblastoma
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