Chronic CED of TPT for Recurrent Malignant Glioma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorJeffrey N. Bruce
About this trial
The primary goal of this study is to establish the safety of chronic Convection Enhanced Delivery (CED) of the chemotherapeutic drug Topotecan for patients with recurrent malignant glioma that harbors the Isocitrate Dehydrogenase mutation (IDH-mut). The secondary goal of the study is to study drug distribution and assess the tumor response to prolonged continuous CED of Topotecan.
Convection Enhanced Delivery is a novel method of drug delivery that allows administration of a drug directly to the brain. In CED, a drug pump is placed under the skin in the chest or abdominal region. The pump is connected to a catheter that is tunneled underneath the skin to the brain. The tip of the catheter then infuses Topotecan directly onto the brain tumor. There will be a total of four treatment infusions over the course of 23-29 days, with a 5-7-day rest period between each infusion. Throughout this period, patients' health will be monitored through imaging, blood draws, and regular exams. At the end of the treatment period, the pump will be removed, followed by resection of the tumor. Patients will be followed for the duration of their lives.
This is the investigator's second clinical trial studying CED of TPT in recurrent glioma. In the prior Phase 1b trial, chronic pulsatile CED safely and effectively delivered Topotecan to patients with IDH mutant recurrent Glioblastoma (WHO grade 4).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have recurrent malignant glioma with a history of WHO grade 3-4 IDH-mutant status and evidence of radiographic progression and suspicion of histopathological recurrence. Stereotactic biopsies will be performed to assess the presence of active tumor by frozen section prior to initiating treatment. Patients with a history of WHO grade 2 recurrent glioma, IDH-Mutant, who now demonstrate high-grade features of IDH-mutant WHO grade 3-4 will also be included.
Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible.
An MRI scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be less than 32 cc in total volume as assessed by the principal investigator based on pre-enrollment MRI. The lesion must be stereotactically accessible.
Karnofsky performance score must be greater than or equal to 70.
Disqualifiers
Patients with diffuse subependymal or CSF disease.
Patients with tumors involving the cerebellum or both cerebral hemispheres.
Patients with an active infection requiring treatment or having an unexplained febrile illness.
Patients who are known HIV, Hepatitis B or Hepatitis C positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Topotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. HIV, Hepatitis B and Hepatitis C testing is not required for patients not known to have these infections.
Trial design
Design model
Single group
Treatments tested in this trial
Topotecan
DrugTopotecan (TPT) is a chemotherapeutic agent that is a topoisomerase inhibitor. This intervention is uniquely distinguished through its administration using an externalized catheter and external microinfusion pump (Convection-Enhanced Delivery)
Treatment groups
6 Participants
are divided into 1 treatment groupGroup A: Long-term CED of TopotecanExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety, defined as dose at which all patients have had no greater than grade 2 adverse reactions
The primary outcome of the study is to measure the safety of prolonged CED of Topotecan in patients with recurrent IDH-mutant malignant glioma. Safety is defined as the dose at which all patients have had no greater than grade 2 adverse reactions possibly, probably, or definitely related to CED of Topotecan as measured through physical and neurologic examination, laboratory studies, radiographic studies, and adverse effects, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 out from Grade 1 (mild symptoms) to Grade 5 (death related to adverse event).
Time frame
Up to 29 daysSecondary outcomes
1
Progression Free Survival (PFS), Overall Survival (OS)
Progression Free Survival is defined as the duration of time from start of Topotecan treatment to time of progression or death from any cause, whichever occurs first. Overall survival is defined as the duration of time from the start of Topotecan treatment to death from any cause. Patients will be contacted every 3-6 months, up to 5 years, by phone until death.
Time frame
Up to 5 years2
Tumor Response to Treatment
The response of the tumor to TPT treatment will be measured radiographically with MRI periodically throughout the 23-29 day treatment period and on follow up 4-6 weeks after treatment, per the international criteria proposed by the updated Response Assessment in Neuro-oncology (RANO) guidelines.
Time frame
Up to 29 days of treatment, and 4-6 weeks post treatment period3
Clinical Toxicity Rate
This is defined by the number of serious adverse events occuring, which is projected to be ≤ 5% at 23-29 days. A clinical toxicity rate that exceeds 20% will be considered unacceptable for this procedure.
Time frame
Up to 29 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Jeffrey N. Bruce
Lead sponsor
Columbia University
Sponsor institution
Source ClinicalTrials.gov