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Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma

Primary Purpose

Glioblastoma

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

nelfinavir

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring glioblastoma, nelfinavir, functional imaging, AKT pathway

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Maastricht Radiation Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

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

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.

Full Information

NCT ID

NCT00694837

First Posted

June 9, 2008

Last Updated

April 9, 2015

Sponsor

Maastricht Radiation Oncology

Collaborators

Maastricht University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00694837

Brief Title

Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma

Official Title

Phase I/II Study for Patients With Newly Diagnosed Glioblastoma Testing Nelfinavir in Combination With Concomitant Temozolomide and Radiotherapy.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

March 2009 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maastricht Radiation Oncology

Collaborators

Maastricht University Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

glioblastoma, nelfinavir, functional imaging, AKT pathway

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

nelfinavir

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

fase 1: 6 months after treatment; fase 2: 12 months after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Brigitta Baumert, MD PhD

Organizational Affiliation

Maastricht Radiation Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maastricht Radiation Oncology

City

Maastricht

ZIP/Postal Code

6202 AZ

Country

Netherlands

12. IPD Sharing Statement

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Study With Nelfinavir and Combined Radiochemotherapy for Glioblastoma

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