Glioma
Conditions
Keywords
Topotecan, Convection-Enhanced Delivery
Brief summary
The purpose of this study is to determine if treatment with topotecan by an alternative method, direct delivery into brain tumors, is safe and well tolerated. The Cleveland Multiport Catheter is a new, investigational device that will be used to deliver topotecan into your brain tumor. A second purpose of this study is to determine whether the Cleveland Multiport Catheter can be used effectively and safely to deliver topotecan into your brain tumor. This study will also determine the best dose of topotecan to deliver to your tumor with use of the Cleveland Multiport Catheter and will also examine how your tumor responds to treatment with topotecan.
Detailed description
Primary Objectives * To investigate by MR imaging the spatial and temporal distribution of topotecan in enhancing or nonenhancing bulk tumor 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 Secondary Objectives * To investigate the extent to which backflow may be observed on MRI during CEDmediated 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.
Interventions
DRUGTopotecan (<=8cc)
In predominantly enhancing mass with a volume of 8 cc or less of topotecan administered
DRUGTopotecan (>8cc)
In predominantly enhancing mass with a volume of \> 8 cc of topotecan administered. Initial rate is 0.834ml/hour with an increase to 1.668 ml/hour at the second infusion
an investigational device, will be used to deliver the topotecan
DIAGNOSTIC_TESTMagnetic Resonance Imaging (MRI)
to monitor the infusion of topotecan into the tumor
DRUGLower Does Topotecan
Rate for non-enhancing tumors has an initial dose of 0.29ml/hour
Sponsors
Infuseon Therapeutics, Inc.
Michael Vogelbaum, MD, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There will be 3 arms to this study, and they will accrue independently of each other as they reflect distinctly separable populations of patients with rHGG. Arm 1: Predominantly enhancing mass with volume of 8 cc or less. Arm 2: Predominantly enhancing mass with volume of \> 8 cc Arm 3: Predominantly non-enhancing mass
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * Karnofsky Performance Status 70-100 * MRI demonstration of a stereotactically accessible enhancing mass that does not require resection to relieve clinically significant mass effect * Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent * Laboratory values within the following ranges: * Absolute neutrophil count (ANC) ≥ 1,500 / μL * Platelet count ≥ 100,000 / μL * Hemoglobin ≥ 10 g / dL * prothrombin time (PT) / partial thromboplastin time (PTT) not above institutional norms * Estimated glomerular filtration rate (eGFR) of at least 50 mL/min
Exclusion criteria
* Patient is mentally or legally incapacitated at the time of the study * Known HIV(+) or has been diagnosed with AIDS * Participation in another investigational drug study in the prior 4 weeks * Positive pregnancy test in a female * Patient, in the opinion of the investigator, is likely to be poorly compliant * Diffuse subependymal or cerebrospinal fluid (CSF) disease * Tumors involving the cerebellum * Tumor enhancement involving both hemispheres * Active infection requiring treatment * Unexplained febrile illness * Radiation or chemotherapy within 4 weeks of enrollment * Systemic diseases associated with unacceptable anesthesia or operative risk * Inability to undergo magnetic resonance imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion duration, as determined by MRI scan | Up to 12 months | — |
| Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using three-dimensional image reconstruction, as determined by MRI scan | Up to 12 months | — |
| Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion concentration, as determined by MRI scan | Up to 12 months | — |
| Change in the spatial distribution of intratumorally-administered topotecan at serial timepoints using a gadolinium-based contrast agent, as determined by MRI scan | Up to 12 months | — |
| Number of intra-operative catheter related complications | Up to 12 months | Documentation of possible, probable, or definite catheter-related complications |
| Number of post-operative catheter related complications | Up to 12 months | Documentation of possible, probable, or definite catheter-related complications |
| Number of catheter related complications after catheter removal | Up to 12 months | Documentation of possible, probable, or definite catheter-related complications |
| Changes in the spatial distribution of intratumorally-administered topotecan associated with changes in the infusion rate, as determined by MRI scan | Up to 12 months | — |
| Changes in the spatial distribution of intratumorally-administered topotecan at serial timepoints using volumetric magnetic resonance imaging, as determined by MRI scan | Up to 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety as measured by the common terminology criteria for adverse events (CTCAE) | Up to 12 months | Safety will be determined through adverse events by arm |
| Number of Participants with response as measured by the Response Assessment in Neuro-Oncology (RANO) Criteria | Up to 12 months | Response includes objective response rate (ORR), median progression-free survival (PFS), proportion progression-free at six months (PFS-6), and median overall survival (OS) |
Outcome results
None listed