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Safety Study of Replication-competent Adenovirus (Delta-24-rgd) in Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01582516
Recruitment Status : Completed
First Posted : April 20, 2012
Last Update Posted : March 9, 2015
Amsterdam UMC, location VUmc
Information provided by (Responsible Party):
C.Dirven, Erasmus Medical Center

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Brain Tumor Recurring Glioblastoma Biological: delta-24-RGD adenovirus Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2010
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Delta24-RGD
Intracerebral slow continuous infusion of study drug in increasing dose
Biological: delta-24-RGD adenovirus
slow continuous microinfusion in and around the brain tumor during 44 4 temporary placed catheters

Primary Outcome Measures :
  1. treatment related serious adverse events [ Time Frame: untill 3 months after treatment ]

Secondary Outcome Measures :
  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. [ Time Frame: 1 year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with histologically proven primary Glioblastoma Multiforme (GBM) will be eligible for this protocol.
  2. 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.
  3. Recurring tumors must either be accessible for surgery, or , when not accessible for surgery meet the following criteria:

    1. unifocal
    2. midline shift < 0.5 cm
    3. no radiological signs of uncal herniation
  4. All recurring tumors must be restricted to one hemisphere, without signs of subependymal spreading.
  5. Before start of virus treatment histological analysis of the resected, or biopsied tumor recurrence must confirm the diagnosis of GBM (based on frozen section).
  6. Patients may or may not have had prior chemotherapy.
  7. 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.
  8. Patients must be > 18 and < 75 years old.
  9. Patients must have a Karnofsky performance status rating > 70 (Appendix 2).
  10. 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.
  11. If sexually active, patients must be willing to use barrier contraception for the duration of the study.
  12. 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

Exclusion Criteria:

  1. 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
  2. Evidence of bleeding diathesis or use of anticoagulant medication.
  3. 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.
  4. 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.
  5. Because of the potential risk of serious infection in immune-compromised individuals, patients known to have HIV infection are excluded.
  6. Patients with a known germline deficit in the retinoblastoma gene or its related pathways.
  7. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01582516

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ERasmus Medical Center
Rotterdam, Netherlands
Sponsors and Collaborators
Erasmus Medical Center
Amsterdam UMC, location VUmc
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Principal Investigator: Clemens Dirven, MD PhD Erasmus Medical Center
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Responsible Party: C.Dirven, MD PhD, Erasmus Medical Center Identifier: NCT01582516    
Other Study ID Numbers: NL24958.000.08
First Posted: April 20, 2012    Key Record Dates
Last Update Posted: March 9, 2015
Last Verified: March 2015
Keywords provided by C.Dirven, Erasmus Medical Center:
brain tumor
replication competent adenovirus
Additional relevant MeSH terms:
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Adenoviridae Infections
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
DNA Virus Infections
Virus Diseases