Clinical trial NCT00308165: Safety Study of Intracerebral Topotecan for Recurrent Brain Tumors
Official title: A Phase I Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Brain Neoplasms, Primary Malignant
Keywords: Recurrent Primary Malignant Brain Tumors
Brain Tumors
Neoplasms, Brain
Brain Cancer
Brain cancer treatment
Topotecan
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2006-03-29
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Time to tumor progression/recurrence
timeFrame: treatment to progression
measure: Time to death
timeFrame: Treatment to time of death
measure: Grade 3 Adverse Events
timeFrame: during treatment, post treatment
Secondary outcomes:
measure: Quality of life at follow-up time points
timeFrame: pre-treatment, during treatment, post treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center Neurological Institute
state: New York
Study officials:
affiliation: Columbia University
name: Jeffrey Bruce, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.