GlioblastomaPhase 1NCT00694837
Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma
A Phase 1 study testing nelfinavir in people with Glioblastoma, run by Maastricht Radiation Oncology at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- nelfinavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2009to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- The opposite from above
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
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.
Read the 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)
- Conditions
- Glioblastoma
- Being tested
- nelfinavir
- Keywords
- glioblastoma, nelfinavir, functional imaging, AKT pathway
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nelfinavirDrug
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 group | Role | What they receive |
|---|---|---|
| B | Experimental | Not described Receives: Drug: nelfinavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Fase 1: after treatment; fase 2: 6 months after treatment
Secondary outcomes (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.
Measured: fase 1: 6 months after treatment; fase 2: 12 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2008 (estimated)
- Study startMar 2009
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht Radiation Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center
- Responsible party
- Sponsor
- Investigators
- Brigitta Baumert, MD PhD, Principal investigator, Maastricht Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00694837
- Sponsor's protocol ID
- 07-09-04/07
- Other IDs
- EudraCT number 2008-001078-34
- Status last verified
- Apr 2015
- First submitted
- 9 Jun 2008
- Last updated
- 10 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.
- ClinicalTrials.gov ID
- NCT00694837
- Acronym / sponsor ID
- 07-09-04/07
- Conditions
- Glioblastoma
- Keywords
- glioblastoma, nelfinavir, functional imaging, AKT pathway
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Maastricht Radiation OncologyUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center
- Study start
- Mar 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 11 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| B | Experimental | Drug: nelfinavir |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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)
Key exclusion criteria (1 listed)
- The opposite from above
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nelfinavirThe 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. | Drug | B |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitta Baumert, MD PhD principal investigator
Maastricht Radiation Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing nelfinavir in people with Glioblastoma, run by Maastricht Radiation Oncology at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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 (time frame: Fase 1: after treatment; fase 2: 6 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2015.