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 Requiring Stereotactic Biopsy (IND 117,240)

IRB INFT1314

CC 14-831

Hospital Main Campus

Stage Stage 3, Stage 4

Disease Brain, Glioblastoma

Drug Topotecan

Description

Description

Primary Objectives

  • To investigate by MR imaging the spatial and temporal distribution of topotecan in tumor and 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.
  • To investigate by MR imaging the influence of the rate and topotecan concentration, on the spatial and temporal distribution of topotecan administered by CED in patients with with recurrent/progressive HGG
  • To evaluate the spatial and temporal distribution of topotecan, by MR imaging, when delivered into enhancing tumor tissue versus non-enhancing tumor tissue (as defined on pre-operative conventional MRI imaging with and without intravenous gadolinium)

Secondary Objectives

  • To investigate the extent to which backflow may be observed on MRI during CED-mediated delivery of topotecan
  • To assess the safety, tolerability and toxicity profile of topotecan administered by CED using different doses and 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 a stereotactic biopsy is indicated for confirmation of recurrence/progression.
  2. Age ≥ 18 years;
  3. Karnofsky Performance Status 70-100;
  4. MRI demonstration of a stereotactically accessible enhancing mass of less than 40 cm3 that does not require resection to relieve clinically significant mass effect;
  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. Tumor enhancement involving both hemispheres;
  9. Active infection requiring treatment;
  10. Unexplained febrile illness;
  11. Radiation or chemotherapy within 4 weeks of enrollment
  12. Systemic diseases associated with unacceptable anesthesia or operative risk;
  13. Inability to undergo magnetic resonance imaging.