Chronic convection-enhanced delivery of topotecan for recurrent IDH‑mutant malignant glioma

Chronic Convection Enhanced Delivery of Topotecan for Recurrent Malignant Glioma

This trial will try giving the chemotherapy drug topotecan directly into the brain with an implanted pump for adults with recurrent IDH‑mutant malignant glioma to see if it is safe and reaches the tumor.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Columbia University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (New York, New York)
• Trial ID: NCT06666712 on ClinicalTrials.gov

What this trial studies

This Phase 1 study tests chronic convection-enhanced delivery (CED) of topotecan using a subcutaneously implanted pump and tunneled catheter placed to infuse drug directly to the tumor site. Treatment consists of four prolonged infusion cycles over 23–29 days with 5–7 day rest periods between infusions, and stereotactic biopsy is used to confirm active tumor before treatment. Patients are monitored with serial MRI, blood draws, and clinical exams to document drug distribution, safety, and tumor response. Eligible tumors must be stereotactically accessible, enhancing on MRI, and under 32 cc, and participants must meet performance-status and prior-treatment requirements.

Who should consider this trial

Good fit: Adults with recurrent IDH‑mutant WHO grade 3–4 malignant glioma who have failed standard treatments, have a stereotactically accessible enhancing lesion under 32 cc, and have a Karnofsky score of ≥70 are ideal candidates.

Not a fit: Patients with IDH‑wildtype tumors, multifocal or very large lesions (>32 cc), significant mass effect, poor functional status, or contraindications to surgery or implanted devices are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could deliver higher concentrations of chemotherapy directly to the tumor while limiting systemic exposure, potentially improving local tumor control with fewer systemic side effects.

How similar studies have performed: Earlier Phase Ib work using chronic pulsatile CED of topotecan showed safe and effective local delivery in recurrent IDH‑wildtype glioblastoma, but applying this approach to IDH‑mutant malignant glioma remains novel and under study.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Patients with recurrent malignant glioma, IDH-mutant, who have failed standard of care treatment are eligible.
3. 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.
4. Karnofsky performance score must be greater than or equal to 70.
5. Men and women of childbearing potential must practice birth control. Women of childbearing potential must have a urine pregnancy test within 7 days of study entry. In accordance with topotecan administration guidelines, women must practice birth control for at least 1 month following chemotherapy infusion. Men must practice birth control for at least four months following termination of chemotherapy infusion.
6. Patients or appropriate legally authorized representatives must possess the ability to give Informed Consent.
7. Patients must be willing to and medically capable of undergoing the surgical operation.
8. Patients must be at least 18 years old.
9. Patients must not have known abnormal organ and marrow function as defined below 14 days or fewer from registration:

   * Leukocytes: ≥3,000/mcL
   * Absolute neutrophil count : ≥1,500/mcL
   * Platelets: ≥100,000/mcL
   * Total bilirubin: within normal institutional limits
   * AST(SGOT)/ALT(SGPT): ≤2.5 × institutional upper limit of normal
   * Creatinine: within normal institutional limits OR
   * Creatinine clearance: ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Exclusion Criteria:

1. Patients with diffuse subependymal or CSF disease.
2. Patients with tumors involving the cerebellum or both cerebral hemispheres.
3. Patients with an active infection requiring treatment or having an unexplained febrile illness.
4. 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.
5. Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
6. Patients who have previously received systemic topotecan for their tumor.
7. Patients who are not able to receive MRI or PET scans.
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds.
9. Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 (CYP) 3A4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong CYP2C8 inhibitors. Patients who are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates are also ineligible. Caution should be used in patients taking other CYP2C8 - or CYP3A4/5-interacting agents as they may increase the serum concentrations of topotecan. If previously on such agents, the patient must discontinue them for at least two weeks prior to study treatment.
10. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing active infection, systemic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
11. Women of childbearing potential who fail to demonstrate a negative pregnancy test 7 or fewer days from registration.
12. Women who are breast-feeding.

Where this trial is running

New York, New York

• Columbia University Irving Medical Center / NewYork-Presbyterian Hospital — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Bruce, MD — Columbia University
• Study coordinator: Jeffrey Bruce, MD

Conditions Brain Tumor, Recurrent; Malignant Glioma; IDH1/IDH2 Mutation; Brain Tumors; topotecan; Convection-Enhanced Delivery; Glioma; IDH Mutation