Details

Details

Title A Pilot Trial of Intraparenchymally-Administered Topotecan using Convection-Enhanced Delivery (CED) in Patients with Suspected Recurrent/Progressive WHO Grade III or IV (High Grade) Glioma Undergoing A Clinically-Indicated Surgical Resection (IND 117,240)

IRB INFT1315

CC 15-614

Hospital Main Campus

Disease Brain, Glioma

Drug Topotecan

Description

Description

Primary Objectives
  • To investigate by MR imaging the spatial and temporal distribution of topotecan in tumor-infiltrated brain administered by convection-enhanced delivery (CED) in patients with recurrent/progressive WHO grade III or IV (high grade) glioma (HGG) who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy, following a clinically-indicated resection of the contrast enhancing tumor mass.
  • To investigate by MR imaging the influence of catheter positioning, on the spatial and temporal distribution of topotecan administered by CED in patients with recurrent/progressive HGG.
  • To evaluate the extent of spatial distribution of topotecan, by MR imaging, when delivered into non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium) in the intraoperative setting, the immediate peri-operative setting, and in the post-operative setting.
Secondary Objectives
  • To investigate the extent to which CED-mediated delivery of topotecan
  • To investigate the extent to which infusate can be distributed in the 2 cm margin around the resection cavity by administration by CED
  • To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different infusion rates.
  • To observe evidence of activity of single-agent topotecan administered by CED to patients with recurrent/progressive HGG who have failed standard therapy comprising surgical biopsy and/or resection and adjuvant chemotherapy and radiotherapy.
Inclusion Criteria

Inclusion Criteria

  1. Histologically confirmed diagnosis of supratentorial WHO Grade III or IV Glioma (High Grade Glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and surgical resection of the enhancing tumor is clinically indicated.
  2. Age ≥18 years;
  3. Karnofsky Performance Status 70-100;
  4. MRI demonstration of an enhancing mass of more than 1 cm3 and less than 100 cm3;
  5. Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent; and
  6. Laboratory values within the following ranges:
    • Absolute neutrophil count (ANC) ≥ 1,500 / μL;
    • Platelet count ≥ 100,000 / μL;
    • Hemoglobin ≥ 10 g / dL;
    • Normal PT/PTT
    • Estimated glomerular filtration rate (eGFR) of at least 50 mL/min
Exclusion Criteria

Exclusion Criteria

  1. Patient is mentally or legally incapacitated at the time of the study;
  2. Known HIV(+) or has been diagnosed with AIDS;
  3. Participation in another investigational drug study in the prior 4 weeks;
  4. Positive pregnancy test in a female;
  5. Patient, in the opinion of the investigator, is likely to be poorly compliant.
  6. Diffuse subependymal or CSF disease;
  7. Tumors involving the cerebellum
  8. Active infection requiring treatment;
  9. Unexplained febrile illness;
  10. Radiation or chemotherapy within 4 weeks of enrollment
  11. Systemic diseases associated with unacceptable anesthesia or operative risk;
  12. Inability to undergo magnetic resonance imaging.