Chronic Convection Enhanced Delivery of Topotecan
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|ClinicalTrials.gov Identifier: NCT03154996|
Recruitment Status : Recruiting
First Posted : May 16, 2017
Last Update Posted : February 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Gliomas||Drug: Topotecan Drug: Gadolinium Device: Synchromed II infusion pumps||Phase 1|
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 central nervous system (CNS) diseases currently limited by drug delivery barriers.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Chronic Convection Enhanced Delivery of Topotecan for Recurrent High Grade Gliomas|
|Actual Study Start Date :||January 18, 2018|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
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.
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)
Other Names: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: GadoDevice: Synchromed II infusion pumps
Implanted subcutaneously to facilitate chronic infusion.
- 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.
- 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: Every 3-6 months, 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03154996
|Contact: Jeffrey Bruce, MDfirstname.lastname@example.org|
|Contact: Laura Good, RNemail@example.com|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Laura Good, RN firstname.lastname@example.org|
|Principal Investigator: Jeffery Bruce, MD|
|Principal Investigator:||Jeffrey Bruce, MDemail@example.com|