Convection-enhanced delivery of topotecan and dexamethasone for malignant gliomas

This technology is a therapeutic strategy for treating brain tumors by using chronic convection-enhanced delivery (CCED) to administer a synergistic combination of topotecan and dexamethasone directly into the brain.

Unmet Need: Targeted, chronic drug delivery for treating brain tumors

Systemic chemotherapy for brain tumors is often ineffective due to the blood-brain barrier and can cause significant toxicity. Although local drug delivery can bypass this barrier, existing convection-enhanced delivery methods rely on external catheters. The risk of infection or inflammation during the process of catheter insertion limits treatment to a single, short-duration infusion. These challenges prevent the sustained, high-concentration, and repeatable drug administration required to effectively treat aggressive brain cancers like glioblastoma.

The Technology: Local topotecan-dexamethasone co-infusion for safer, effective glioma therapy

This strategy utilizes a subcutaneously implantable pump-catheter system for chronic convection-enhanced delivery (CCED) to infuse the chemotherapy drug topotecan in combination with the anti-inflammatory drug dexamethasone directly to the tumor site. This approach bypasses the blood-brain barrier, allowing for repeated, extended infusions that achieve significantly higher drug concentrations at the tumor while avoiding systemic toxicity. The local co-administration of these two agents leads to more effective killing of tumor cells while simultaneously reducing treatment-induced inflammation.

This therapeutic strategy has demonstrated efficacy in preclinical brain tumor animal models. The underlying chronic delivery system has been validated for safety and efficacy in large animal models and has been successfully used in a Phase 1b clinical trial to deliver topotecan to patients with recurrent glioblastoma.

Applications:

• Local treatment of malignant gliomas
• Adjuvant therapy post-tumor resection
• Combination therapy with radiation or immunotherapy
• Drug-delivery kits/systems for gene therapies
• Research tool to study local chemo–steroid efficacy, pharmacokinetics, and pharmacodynamics

Advantages:

• High intratumoral topotecan exposure with low systemic exposure
• Limits local treatment-related inflammation and edema
• Enables repeatable, chronic dosing cycles via an implantable pump
• Precise control of infusion rate, pressure, and scheduled cycles for patient-specific dosing
• Supports imaging-guided planning and monitoring
• Targets tumor and peritumoral margins directly
• Integrates with established CED hardware and workflows

Lead Inventor:

Peter Canoll, M.D., Ph.D.

Patent Information:

Patent Pending

Related Publications:

• D'Amico RS, Neira JA, Yun J, Alexiades NG, Banu M, Englander ZK, Kennedy BC, Ung TH, Rothrock RJ, Romanov A, Guo X, Zhao B, Sonabend AM, Canoll P, Bruce JN. “Validation of an effective implantable pump-infusion system for chronic convection-enhanced delivery of intracerebral topotecan in a large animal model.” J Neurosurg. 2019 Aug 2;133(3):614-623

• Spinazzi EF, Argenziano MG, Upadhyayula PS, Banu MA, Neira JA, Higgins DMO, Wu PB, Pereira B, Mahajan A, Humala N, Al-Dalahmah O, Zhao W, Save AV, Gill BJA, Boyett DM, Marie T, Furnari JL, Sudhakar TD, Stopka SA, Regan MS, Catania V, Good L, Zacharoulis S, Behl M, Petridis P, Jambawalikar S, Mintz A, Lignelli A, Agar NYR, Sims PA, Welch MR, Lassman AB, Iwamoto FM, D'Amico RS, Grinband J, Canoll P, Bruce JN. “Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial.” Lancet Oncol. 2022 Nov;23(11):1409-1418

• Ung TH, Malone H, Canoll P, Bruce JN. Convection-enhanced delivery for glioblastoma: targeted delivery of antitumor therapeutics. CNS Oncol. 2015;4(4):225-34.

• Yun J, Rothrock RJ, Canoll P, Bruce JN. “Convection-enhanced delivery for targeted delivery of antiglioma agents: the translational experience.” J Drug Deliv. 2013;2013:107573.

Tech Ventures Reference:

• IR CU18338

• Licensing Contact: Dovina Qu