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

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ClinicalTrials.gov Identifier: NCT01582516
Recruitment Status : Completed
First Posted : April 20, 2012
Last Update Posted : March 9, 2015
Sponsor:
Collaborator:
VU University Medical Center
Information provided by (Responsible Party):
C.Dirven, Erasmus Medical Center

Tracking Information
First Submitted Date  ICMJE April 19, 2012
First Posted Date  ICMJE April 20, 2012
Last Update Posted Date March 9, 2015
Study Start Date  ICMJE June 2010
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2012)
treatment related serious adverse events [ Time Frame: untill 3 months after treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01582516 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2012)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2012)
survival [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Replication-competent Adenovirus (Delta-24-rgd) in Patients With Recurrent Glioblastoma
Official Title  ICMJE A Phase I/II Trial of a Conditionally Replication-competent Adenovirus (Delta-24-rgd) Administered by Convection Enhanced Delivery in Patients With Recurrent Glioblastoma
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor
  • Recurring Glioblastoma
Intervention  ICMJE Biological: delta-24-RGD adenovirus
slow continuous microinfusion in and around the brain tumor during 44 hrs.by 4 temporary placed catheters
Study Arms  ICMJE Experimental: Delta24-RGD
Intracerebral slow continuous infusion of study drug in increasing dose
Intervention: Biological: delta-24-RGD adenovirus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2015)
20
Original Estimated Enrollment  ICMJE
 (submitted: April 19, 2012)
30
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01582516
Other Study ID Numbers  ICMJE NL24958.000.08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party C.Dirven, Erasmus Medical Center
Study Sponsor  ICMJE Erasmus Medical Center
Collaborators  ICMJE VU University Medical Center
Investigators  ICMJE
Principal Investigator: Clemens Dirven, MD PhD Erasmus Medical Center
PRS Account Erasmus Medical Center
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP