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Chronic Convection Enhanced Delivery of Topotecan

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified May 2017 by Jeffrey N. Bruce, Columbia University
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jeffrey N. Bruce, Columbia University
ClinicalTrials.gov Identifier:
NCT03154996
First received: May 14, 2017
Last updated: May 18, 2017
Last verified: May 2017
  Purpose
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).

Condition Intervention Phase
Gliomas Drug: Topotecan Drug: Gadolinium Device: Synchromed II infusion pumps Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chronic Convection Enhanced Delivery of Topotecan for Recurrent High Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Jeffrey N. Bruce, Columbia University:

Primary Outcome Measures:
  • Dose at which all patients have had no greater than grade 2 adverse reactions [ Time Frame: Up to 29 days ]
    This is designed to measure the safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients.


Secondary Outcome Measures:
  • Clinical toxicity rate [ Time Frame: Up to 29 days ]
    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.

  • Change in radiographic tumor response [ Time Frame: Baseline, 6 weeks post-treatment ]
    Tumor response to TPT will be investigated by MRI scan.

  • Progression free survival (PFS) [ Time Frame: Up to 5 years ]
    The length of time during and after the treatment of disease that a patient lives with the disease but it does not get worse. Patients will be contacted every 3-6 months, up to 5 years, by phone until death.


Estimated Enrollment: 20
Anticipated Study Start Date: June 2017
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Short term CED of Topotecan
A series of 5 patients with recurrent HGGs will be recruited for a study in which TPT and Gadolinium will be co-delivered by CED prior to surgical resection four days later.
Drug: Topotecan

Topotecan is a chemotherapeutic agent that is a topoisomerase inhibitor. TPT is administered through an externalized catheter and external microinfusion pump.

Dose: 146 uM

Other Names:
  • Hycamtin
  • TPT
Drug: Gadolinium
Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.
Other Name: Gado
Experimental: Long term CED of Topotecan
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

Topotecan is a chemotherapeutic agent that is a topoisomerase inhibitor. TPT is administered through an externalized catheter and external microinfusion pump.

Dose: 146 uM

Other Names:
  • Hycamtin
  • TPT
Drug: Gadolinium
Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.
Other Name: Gado
Device: Synchromed II infusion pumps
FDA-approved for the treatment of spasticity and chronic pain, will be implanted subcutaneously to facilitate chronic infusion.

Detailed Description:

Malignant gliomas are among the most pernicious of human tumors - locally invasive and universally recurrent, with recurrence usually occurring within two centimeters of the original resection cavity. Although numerous chemotherapeutic drugs demonstrate significant anti-tumor activity in preclinical studies, the efficacy in clinical trials has been dismal because systemic delivery fails to achieve therapeutic drug levels in tumor cells due to various factors including limited blood-brain barrier permeability and systemic toxicity.

Convection-enhanced delivery (CED) is a method of regional drug delivery that circumvents this problem. Phase 1 clinical trial has shown that a potent topoisomerase inhibitor, topotecan (TPT), can be safely and effectively delivered by CED into patients with recurrent malignant gliomas. This study will expand on these clinical results to address two current limitations to the clinical application of CED: 1) A reliable method for non-invasively monitoring drug distribution throughout the tumor and brain does not exist; and 2) Duration of CED therapy has been limited to short-term infusions secondary to the use of externalized infusion pumps.

The hypothesis is that extended chronic local-regional delivery of TPT is safe, effective and feasible in patients with recurrent gliomas. TPT will be directly and chronically delivered into the tumor and surrounding brain by CED through subcutaneously implanted pumps while innovating a methodology for monitoring the drug distribution through non-invasive imaging. This strategy will overcome the limitations of chemotherapy as currently used in the treatment of gliomas, and may be applicable to other CNS diseases currently limited by drug delivery barriers.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a recurrent malignant glioma (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 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 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/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:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03154996

Contacts
Contact: Jeffery Bruce, MD 212-305-7346 jnb2@cumc.columbia.edu
Contact: Laura Good, RN lg2824@cumc.columbia.edu

Locations
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Laura Good, RN       lg2824@cumc.columbia.edu   
Principal Investigator: Jeffery Bruce, M.D.         
Sponsors and Collaborators
Jeffrey N. Bruce
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jeffery Bruce, MD jnb2@cumc.columbia.edu
  More Information

Additional Information:
Responsible Party: Jeffrey N. Bruce, Edgar M. Housepian Professor of Neurological Surgery Research at, Dept of Neurological Surgery, Columbia University
ClinicalTrials.gov Identifier: NCT03154996     History of Changes
Other Study ID Numbers: AAAQ9520
5R01CA161404-02 ( U.S. NIH Grant/Contract )
Study First Received: May 14, 2017
Last Updated: May 18, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeffrey N. Bruce, Columbia University:
Gliomas
Recurrent
Chronic Convection
High Grade Gliomas

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 20, 2017