Safety Study of Intracerebral Topotecan for Recurrent Brain Tumors

• ClinicalTrials.gov Identifier: NCT00308165
• Recruitment Status: Unknown
• First Posted: March 29, 2006
• Last Update Posted: January 15, 2015
• Sponsor: Jeffrey N. Bruce
• Information provided by (Responsible Party): Jeffrey N. Bruce, Columbia University

Study Description

Brief Summary:

This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.

This study will also evaluate advanced magnetic resonance (MR) imaging techniques.

The study will assess quality of life parameters throughout the follow-up period.

Condition or disease	Intervention/treatment	Phase
Brain Neoplasms, Primary Malignant	Procedure: Convection-Enhanced Delivery; Drug: Topotecan	Phase 1; Phase 2

Detailed Description:

Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.

Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.

Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors
• Study Start Date: March 2004
• Actual Primary Completion Date: September 2011
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm

Intervention/treatment

Experimental: Topotecan; Once a plastic catheter is placed, within 24 hours of placement, the catheter will be connected to a small pump at the bedside, and the convection-enhanced delivery of the Topotecan will begin. The Topotecan will be infused for 4 to 5 days after which time the catheters will simply be pulled out. Patients will be monitored with blood tests and MRI scans during the treatment and at different time periods during the following months.

Procedure: Convection-Enhanced Delivery; microinfusion pumps to deliver chemotherapy directly into brain tumors; Other Name: Intracerebral Clysis; Drug: Topotecan; chemotherapeutic drug for the treatment of brain tumors; Other Name: Hycamtin

Outcome Measures

Primary Outcome Measures :

1. Time to tumor progression/recurrence [ Time Frame: treatment to progression ]
2. Time to death [ Time Frame: Treatment to time of death ]
3. Grade 3 Adverse Events [ Time Frame: during treatment, post treatment ]

Secondary Outcome Measures :

1. Quality of life at follow-up time points [ Time Frame: pre-treatment, during treatment, post treatment ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Single primary malignant brain tumor
• Previous treatment with external beam radiation
• Tumor is stereotactically accessible
• Karnofsky Performance Score of at least 60

Exclusion Criteria:

• Diffuse subependymal or Cerebrospinal fluid (CSF) disease
• Tumor involves brainstem, cerebellum or both hemispheres
• Active infection
• Systemic disease associated with unacceptable anesthetic/operative risk
• Previous treatment with topotecan
• Unable to receive MRI scans

Contacts and Locations

Locations

United States, New York

Columbia University Medical Center Neurological Institute

New York, New York, United States, 10032

Sponsors and Collaborators

Jeffrey N. Bruce

Investigators

• Principal Investigator: Jeffrey Bruce, MD; Columbia University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Anderson RC, Kennedy B, Yanes CL, Garvin J, Needle M, Canoll P, Feldstein NA, Bruce JN. Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J Neurosurg Pediatr. 2013 Mar;11(3):289-95. doi: 10.3171/2012.10.PEDS12142. Epub 2012 Dec 14.

• Responsible Party: Jeffrey N. Bruce, Edgar M. Housepian Professor of Neurological Surgery Research, Columbia University
• ClinicalTrials.gov Identifier: NCT00308165
• Obsolete Identifiers: NCT00324844, NCT00452959
• Other Study ID Numbers: AAAA4229; R01CA089395 ( U.S. NIH Grant/Contract )
• First Posted: March 29, 2006
• Last Update Posted: January 15, 2015
• Last Verified: January 2015

Keywords provided by Jeffrey N. Bruce, Columbia University:

Recurrent Primary Malignant Brain Tumors; Brain Tumors; Neoplasms, Brain; Brain Cancer; Brain cancer treatment; Topotecan

Additional relevant MeSH terms:

Brain Neoplasms; Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Topotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents