Chronic Convection Enhanced Delivery of Topotecan

NCT03154996 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AAAQ95205R01CA161404-02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this study is to establish, for the first time, safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients with recurrent high grade glioma (HGG). Secondary objectives will include determination of topotecan (TPT) distribution and radiographic tumor response with prolonged continuous intracerebral convection-enhanced delivery (CED).

Conditions

Gliomas

Keywords

Gliomas; Recurrent; Chronic Convection; High Grade Gliomas

Outcome Measures

Primary Outcomes (1)

• Dose at which all patients have had no greater than grade 2 adverse reactions

  This is designed to measure the safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients.

  Up to 29 days

Secondary Outcomes (3)

• Clinical toxicity rate

  Up to 29 days

• Change in radiographic tumor response

  Baseline, 6 weeks post-treatment

• Progression free survival (PFS)

  Every 3-6 months, up to 5 years

Study Arms (1)

Long term CED of Topotecan

EXPERIMENTAL

An additional 5 patients will be treated with TPT by CED maintained for 32 days. TPT infusions will be carried out for 32 days using Synchromed II infusion pumps with the same infusion parameters and experimental conditions used in the short term studies.

Drug: Topotecan; Drug: Gadolinium; Device: Synchromed II infusion pumps

Interventions

Topotecan DRUG

Topotecan is a chemotherapeutic agent that is a topoisomerase inhibitor. TPT is administered through an externalized catheter and external microinfusion pump. Dose: 146 micrometers (uM)

Also known as: Hycamtin, TPT

Long term CED of Topotecan

Gadolinium DRUG

Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.

Also known as: Gado

Long term CED of Topotecan

Synchromed II infusion pumps DEVICE

Implanted subcutaneously to facilitate chronic infusion.

Long term CED of Topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a recurrent malignant glioma (World Health Organization (WHO) grade III-IV), including recurrent glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma. Stereotactic biopsies will be performed to confirm this diagnosis prior to initiating the treatment.
• Patients with tumors of the brain must have been previously treated with surgical resection, external beam radiation, and temozolomide chemotherapy.
• An magnetic resonance (MR) 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. The lesion must be stereotactically accessible.
• Patients must have demonstrated evidence of increasing contrast enhancement on MR or computed tomography (CT) imaging while on stable or increasing dose of steroid.
• Karnofsky performance score of greater than or equal to 60.
• Men and women of childbearing potential must practice birth control. Women of child bearing potential must have a urine pregnancy test within 7 days of study entry.
• Patients must possess the ability to give Informed Consent.
• Patients must be willing to and medically capable of undergoing the surgical operation.
• There is no upper age limit. Patients at extreme upper end of the age spectrum will not be automatically excluded, but will be carefully scrutinized to determine their suitability for this procedure.
• Patients must be at least 18 years old.
• Patients must have normal organ and marrow function as defined below:
• Leukocytes: ≥3,000/ cells per microliter of blood (mcL)
• Absolute neutrophil count: ≥1,500/mcL
• Platelets: ≥100,000/mcL
• Total bilirubin: within normal institutional limits

You may not qualify if:

• Patients with diffuse subependymal or cerebral spinal fluid (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.
• Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
• Patients who have previously received systemic topotecan for their tumor
• Patients who are not able to receive an MRI scan.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• 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. doi: 10.1016/S1470-2045(22)00599-X. Epub 2022 Oct 13.

  PMID: 36243020 DERIVED

Related Links

• Herbert Irving Comprehensive Cancer Center clinical trials online search tool

MeSH Terms

Conditions

Glioma; Recurrence

Interventions

Topotecan; 9 alpha,11 alpha,15 alpha-trihydroxy-16-phenoxy-17,18,19,20-tetranorprosta-4,5,13-trienoic acid; Gadolinium

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Metals

Study Officials

• Jeffrey Bruce, MD

  jnb2@cumc.columbia.edu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2017
• First Posted: May 16, 2017
• Study Start: January 18, 2018
• Primary Completion: August 20, 2021
• Study Completion: August 20, 2021
• Last Updated: April 22, 2026

Record last verified: 2022-06

Locations

US (1)