A Dose Escalation Phase I Study Of Human- Recombinant Bone Morphogenetic Protein 4 Administrated Via CED In GBM Patients
Condition: Glioblastoma
MeSH terms: Glioblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to evaluate the feasibility and safety of intra-tumor and
      interstitial therapy with hBMP4 in increasing doses in patients with progressive and/or
      multiple recurrent Glioblastoma multiforme (GBM).
    

Detailed description: 
      This multicentre, open-label, dose escalating, Phase I study will enrol approximately 18
      patients with progressive and/or multiple recurrent GBM, who after failure of standard
      therapies will receive GMP Human- recombinant Bone Morphogenetic Protein 4 via intra-tumour
      and interstitial delivery by CED.

      Patients will undergo a resection or biopsy of the tumour, confirmation of viable malignant
      glioma tumour cells during frozen section performed by the institutional pathologists, and
      intra-tumor and interstitial placement under neuronavigational guidance of 2 or 3 catheters.
      No catheters will be placed at time of resection. After resection, catheters will be placed
      during a separate procedure several days later based upon the patient's condition as
      determined by both a clinical examination and routine MRI scan.

      Patients will receive intra-tumour and interstitial CED of increasing amounts of hrBMP4
      solutions (at a starting dose of 0.5 mg) and 1:70 gadolinium-diethylenetriamine pentaacetic
      acid (Gd-DTPA) in a total of 44-66 ml over up to 4-6 days at the discretion of the
      investigator.

      Gd-DTPA will be co-infused with hrBMP4 to determine the extent of intra-tumour and
      interstitial drug delivery. Patients will be hospitalized from the time of the original
      surgery until the end of infusion of hrBMP4.

      Patients will be followed for the duration of the study. The primary endpoint of the study is
      monitoring feasibility and patient safety for the incidence of Dose-Limiting Toxicity (DLT)
      following intra-tumour and interstitial therapy with hrBMP4 and to determine whether there is
      a Maximum Tolerated Dose (MTD).
    

Intervention name(s): hrBMP4
Intervention type(s): Drug
Intervention description(s): Patients will undergo a resection or biopsy of the tumour, confirmation of viable malignant glioma tumour cells and intratumour/interstitial placement under neuronavigational guidance of 2 or 3 catheters.
Catheters will be placed during a second procedure a few days later based upon the patient's condition.
Patients will receive intra-tumour and interstitial CED of increasing amounts of hrBMP4 solutions (starting dose of 0.5 mg) and 1:70 gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) in a total of 44-66ml over up to 4-6 days. Gd-DTPA will be co-infused with BMP4 to determine the extent of intra-tumour and interstitial drug delivery. HrBMP4 will be delivered as a continuous infusion via the intracranial catheters.
Other intervention name(s): Recombinant Bone Morphogenic Protein-4; Device:Intracranial Catheter
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: A malignant growing astrocytoma of central nervous system