Phase I/II study for patients with newly diagnosed glioblastoma testing nelfinavir in combination with concomitant temozolomide and radiotherapy.

Recruiting

• Conditions: glioblastoma; 10029211

• Registration Number: NL-OMON32210
• Lead Sponsor: Academisch Ziekenhuis Maastricht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 58

Inclusion Criteria

Histological confirmed glioblastoma multiforme at primary diagnosis
Tumours which do enhance on pre-operative imaging
Age >=18-70
WHO performance status 0-2, RTOG- RPA class III-IV.
No recent (< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
Willing and able to comply with the study prescriptions
Have given written informed consent before patient registration
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 uncontrolled infectious disease
No use of terfenadine, astemizol, cisapride, sildenafil, lovastatin or simvastatin
No 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 (lovastatin, simvastatin, atorvastatin), rifampin, rifabutin, felodipine, nifedipine, and sildenafil or St. John's wort.
Adequate haematological, renal and hepatic function
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

Exclusion Criteria

the opposite of the above

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase I:<br /><br>Primary: To determine the MTD of nelfinavir as an adjuvant in the<br /><br>radiochemotherapy treatment in primary glioblastoma patients by assessing the<br /><br>incidence of any grade 3 or higher non-haematological or grade 4 or higher<br /><br>haematological acute toxicity (CTCAE v3.0), excluding toxicities that can be<br /><br>expected from the standard treatment of chemoradiotherapy with temozolomide.<br /><br><br /><br>Phase II<br /><br>Primary: PFS at 6 months</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase I:<br /><br>Secondary:<br /><br>• Incidence of other acute toxicity, assessed according to CTCv3.0.<br /><br>• 6- months progression free survival<br /><br>• Overall survival<br /><br>• Metabolic ratios of standardized uptake value (SUV) of serial 18F-FDG:<br /><br>assessed by PET-CT.<br /><br>• Perfusion measurements (rCBV) with Perfusion MRI<br /><br><br /><br>Phase II:<br /><br>Secondary:<br /><br>• Progression free survival at 12 months<br /><br>• Overall survival<br /><br>• Incidence of acute toxicity, assessed according to CTCv3.0.<br /><br>• Metabolic ratios of standardized uptake value (SUV) of serial 18F-FDG:<br /><br>assessed by PET-CT.<br /><br>• Phosphorylation of AKT in tumour tissue before treatment</p><br>