Brain TumorPhase 1/2NCT01582516
Safety Study of Replication-competent Adenovirus (Delta-24-rgd) in Patients With Recurrent Glioblastoma
A Phase 1/2 study testing delta-24-RGD adenovirus in people with Brain Tumor and Recurring Glioblastoma, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
In the Netherlands a 2 center investigator-driven phase I/II clinical trial is initiated in June 2010 testing the oncolytic adenovirus Delta24-RGD to treat glioblastoma patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Brain Tumor, Recurring Glioblastoma
- What is being tested?
- delta-24-RGD adenovirus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2010to Dec 2014
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically proven primary Glioblastoma Multiforme (GBM) will be eligible for this protocol.
- Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan within 3 weeks prior to registration after failing prior resection (surgery or biopsy) and/ or chemo- and/or radiation therapy.
- Recurring tumors must either be accessible for surgery, or , when not accessible for surgery meet the following criteria:
- unifocal
- midline shift < 0.5 cm
- no radiological signs of uncal herniation
Show all 21Show fewer
- All recurring tumors must be restricted to one hemisphere, without signs of subependymal spreading.
- Before start of virus treatment histological analysis of the resected, or biopsied tumor recurrence must confirm the diagnosis of GBM (based on frozen section).
- Patients may or may not have had prior chemotherapy.
- Patients must be able to read and understand the informed consent document and must sign and date the informed consent. Procedures to obtain such informed consent should be according to ICH-GCP, the local regulatory requirement and the rules followed at the institute.
- Patients must be > 18 and < 75 years old.
- Patients must have a Karnofsky performance status rating > 70 (Appendix 2).
- Patients must have recovered from the toxic effects of prior therapy. For example, they must be at least two weeks after vincristine, 6 weeks after nitrosoureas, 3 weeks after procarbazine or temozolomide administration, and 6 weeks after radiation therapy.
- If sexually active, patients must be willing to use barrier contraception for the duration of the study.
- Patients must have adequate hepatic, renal and bone marrow function, defined as
- absolute neutrophil count (ANC) > 1,5* 109/L
- platelet count of > 100* 109/L
- ALT (SGPT), AST (SGOT) and Alkaline Phosphatase < 2 times ULN
- total bilirubin <1.5 mg/dL
- creatinine <1.5 times ULN
- urea (BUN) <1.5 times ULN
Who cannot join
- Patients with active uncontrolled infection. Upper pulmonary infection and flu-like signs or presence of adenovirus in pre-operative throat-swab or serum sample as determined by PCR. All patients must be afebrile (<38.0 C) at the start of therapy
- Evidence of bleeding diathesis or use of anticoagulant medication.
- Patients with systemic diseases or other unstable conditions which may be associated with unacceptable anesthetic/ operative risk and/or which would not allow safe completion of this study protocol, e.g. uncontrolled seizures.
- Because of the potential risk of a recombinant virus containing a gene involved in cellular growth regulation and differentiation which could potentially affect a developing fetus or growing infant, females who are pregnant, at risk of pregnancy, or breast feeding a baby during the study period are excluded.
- Because of the potential risk of serious infection in immune-compromised individuals, patients known to have HIV infection are excluded.
- Patients with a known germline deficit in the retinoblastoma gene or its related pathways.
- Patients with other primary malignancy than GBM. However, patients with curatively treated carcinoma-in situ or basal cell carcinoma or patients who have been disease free for at least 2 years and not using any anti-cancer therapy, are eligible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Trial of a Conditionally Replication-competent Adenovirus (Delta-24-rgd) Administered by Convection Enhanced Delivery in Patients With Recurrent Glioblastoma
In the Netherlands a 2 center investigator-driven phase I/II clinical trial is initiated in June 2010 testing the oncolytic adenovirus Delta24-RGD to treat glioblastoma patients. The virus is administrated using convection-enhanced delivery by 4 catheters as delivery technique, targeting solid tumor as well as infiltrated tumor cells within the peri-tumoral brain. Patients will be enrolled in cohorts of 3 per dose-level. The dose levels to be explored are: 10^7, 10^8, 10^9, 10^10, 3*10^10 and 10^11 viral particles (vp). Once the MTD has been determined, or the study has reached the highest dose cohort, a further 6 or 9 patients will be enrolled at the MTD and evaluated for safety and preliminary signs of efficacy, such that in total at least 12 patients have received the MTD.
The primary objective is to determine the safety and tolerability of Delta-24-RGD administered by CED to the tumor and the surrounding infiltrated brain in patients with recurrent GBM. Secondary objectives are to determine the Progression Free Survival (PFS), Overall Survival (OS), and tumor response rate in patients with recurring tumors amenable for surgical resection and treated at the MTD.
Read more
Cerebrospinal fluid as well as brain interstitial fluid by microdialysis next to the routinely collected samples of blood at various timepoints before, during and after virus infusion. Various neurodegenerative biomarkers as well as markers of immune response will be assessed in these samples.
Furthermore extensive sampling and PCR analyses will be performed to evaluate distribution and shedding of the virus.
- Conditions
- Brain Tumor, Recurring Glioblastoma
- Being tested
- delta-24-RGD adenovirus
- Keywords
- brain tumor, virotherapy, glioblastoma, replication competent adenovirus
- Medical subject headings
- Brain Neoplasms, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
delta-24-RGD adenovirusBiological
slow continuous microinfusion in and around the brain tumor during 44 hrs.by 4 temporary placed catheters
| Study group | Role | What they receive |
|---|---|---|
| Delta24-RGD | Experimental | Intracerebral slow continuous infusion of study drug in increasing dose Receives: Biological: delta-24-RGD adenovirus |
What is being measured
The primary outcome is the main question the study is designed to answer.
treatment related serious adverse events
Measured: untill 3 months after treatment
Secondary outcomes (1)
The number of participants alive after 6 months and after 1 year : Progression free survival after 6 months and overall survival after 6 months and one year.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study startJun 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC, location VUmc
- Responsible party
- Principal investigator, C.Dirven, Erasmus Medical Center
- Investigators
- Clemens Dirven, MD PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01582516
- Sponsor's protocol ID
- NL24958.000.08
- Status last verified
- Mar 2015
- First submitted
- 19 Apr 2012
- Last updated
- 9 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of a Conditionally Replication-competent Adenovirus (Delta-24-rgd) Administered by Convection Enhanced Delivery in Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT01582516
- Acronym / sponsor ID
- NL24958.000.08
- Conditions
- Brain Tumor, Recurring Glioblastoma
- Keywords
- brain tumor, virotherapy, glioblastoma, replication competent adenovirus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Amsterdam UMC, location VUmc
- Study start
- Jun 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 20 Apr 2012 (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.
In the Netherlands a 2 center investigator-driven phase I/II clinical trial is initiated in June 2010 testing the oncolytic adenovirus Delta24-RGD to treat glioblastoma patients. The virus is administrated using convection-enhanced delivery by 4 catheters as delivery technique, targeting solid tumor as well as infiltrated tumor cells within the peri-tumoral brain. Patients will be enrolled in cohorts of 3 per dose-level. The dose levels to be explored are: 10^7, 10^8, 10^9, 10^10, 3*10^10 and 10^11 viral particles (vp). Once the MTD has been determined, or the study has reached the highest dose cohort, a further 6 or 9 patients will be enrolled at the MTD and evaluated for safety and preliminary signs of efficacy, such that in total at least 12 patients have received the MTD.
The primary objective is to determine the safety and tolerability of Delta-24-RGD administered by CED to the tumor and the surrounding infiltrated brain in patients with recurrent GBM. Secondary objectives are to determine the Progression Free Survival (PFS), Overall Survival (OS), and tumor response rate in patients with recurring tumors amenable for surgical resection and treated at the MTD.
Cerebrospinal fluid as well as brain interstitial fluid by microdialysis next to the routinely collected samples of blood at various timepoints before, during and after virus infusion. Various neurodegenerative biomarkers as well as markers of immune response will be assessed in these samples.
Furthermore extensive sampling and PCR analyses will be performed to evaluate distribution and shedding of the virus.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Delta24-RGD | Experimental | Biological: delta-24-RGD adenovirusIntracerebral slow continuous infusion of study drug in increasing dose |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients with histologically proven primary Glioblastoma Multiforme (GBM) will be eligible for this protocol.
- Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan within 3 weeks prior to registration after failing prior resection (surgery or biopsy) and/ or chemo- and/or radiation therapy.
- Recurring tumors must either be accessible for surgery, or , when not accessible for surgery meet the following criteria:
- All recurring tumors must be restricted to one hemisphere, without signs of subependymal spreading.
- Before start of virus treatment histological analysis of the resected, or biopsied tumor recurrence must confirm the diagnosis of GBM (based on frozen section).
Key exclusion criteria (7 listed)
- Patients with active uncontrolled infection. Upper pulmonary infection and flu-like signs or presence of adenovirus in pre-operative throat-swab or serum sample as determined by PCR. All patients must be afebrile (<38.0 C) at the start of therapy
- Evidence of bleeding diathesis or use of anticoagulant medication.
- Patients with systemic diseases or other unstable conditions which may be associated with unacceptable anesthetic/ operative risk and/or which would not allow safe completion of this study protocol, e.g. uncontrolled seizures.
- Because of the potential risk of a recombinant virus containing a gene involved in cellular growth regulation and differentiation which could potentially affect a developing fetus or growing infant, females who are pregnant, at risk of pregnancy, or breast feeding a baby during the study period are excluded.
- Because of the potential risk of serious infection in immune-compromised individuals, patients known to have HIV infection are excluded.
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 |
|---|---|---|
| delta-24-RGD adenovirusslow continuous microinfusion in and around the brain tumor during 44 hrs.by 4 temporary placed catheters | Biological | Delta24-RGD |
Primary outcome
treatment related serious adverse events
Time frame: untill 3 months after treatment
1 secondary outcome
The number of participants alive after 6 months and after 1 year : Progression free survival after 6 months and overall survival after 6 months and one year.
Time frame: 1 year
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 9 Mar 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.
Clemens Dirven, MD PhD principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing delta-24-RGD adenovirus in people with Brain Tumor and Recurring Glioblastoma, run by Erasmus Medical Center 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 21 inclusion and 7 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 9 Mar 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
treatment related serious adverse events (time frame: untill 3 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 9 Mar 2015.