Intracerebral Clysis in Treating Patients With Recurrent Primary Brain Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Herbert Irving Comprehensive Cancer Center
Information provided by (Responsible Party):
Jeffrey N. Bruce, Columbia University
ClinicalTrials.gov Identifier:
NCT00452959
First received: March 27, 2007
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

Patients will be hospitalized for a Stereotactic biopsy of the recurrent primary brain tumor and then have placement of two catheters into the recurrent brain tumor. Chemotherapy (Topotecan) will be slowly infused through the catheters over 4-5 days. Patients will be followed with daily MRI scans, neurological assessments and blood work throughout the hospitalization. After hospitalization there will be monthly follow-up visits, which progress to every 2 months visits. MRI scan, neurological assessments and blood work will be done at the follow-up visits.


Condition Intervention Phase
Recurrent Anaplastic Astrocytoma
Recurrent Anaplastic Oligodendroglioma
Recurrent Anaplastic Oligo-Astrocytoma
Recurrent Glioblastoma Multiforme
Drug: Topotecan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Topotecan by Intracerebral Clysis for the Treatment of Recurrent Primary Malignant Brain Tumors

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Time to tumor progression [ Time Frame: treatment to tumor progression ] [ Designated as safety issue: No ]
  • Time to death [ Time Frame: treatment to time of death ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: October 2003
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topotecan
Dose escalation
Drug: Topotecan
The starting dose will be 0.02 mg/ml, and the second step will escalate the dosage by 100% (0.04 mg/ml); the third step is 67% greater than the second (0.0667 mg/ml); the fourth step is 50% greater than the third (0.1 mg/ml); and each subsequent step is 33% greater than that preceding it (5th step= 0.133; 6th step= 0.178; 7th step=0.237 mg/ml). The total volume of treatment will be 40 mL which is the volume used in previous human trials with ICC.
Other Name: Topotecan

Detailed Description:

Candidates will be screened with a physical examination, neurological examination, Karnofsky performance status, magnetic resonance imaging (MRI) of the brain, and routine laboratory tests. Eligible candidates will be admitted to the hospital for Stereotactic biopsy of the recurrent brain tumor and then have placement of two catheters into the tumor. It will be followed with 4-5 days of a slow infusion of Topotecan directly into the tumor using the catheter and microinfusion pump. Candidates will be evaluated daily with MRI of the brain and neurological exam. Once the infusion of Topotecan is complete and the catheters are discontinued, the candidate is discharged home in approximately 24 hours. Follow-up visits after hospitalization will be monthly for four visits and then every eight weeks. At each follow-up visit a neurological exam, Karnofsky performance status, routine laboratory tests and a MRI of the brain will be performed.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • Patients with recurrent primary malignant brain tumors.
  • Patient must have been previously treated with external beam radiation, which is the standard of care.
  • An MR scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be ≤ 100cc in total volume. The lesion must be stereotactically accessible.
  • Patient 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 child-bearing potential must practice birth control. Women of child bearing age must have a negative serum or urine pregnancy test within 7 days of study entry.
  • Patient must possess the ability to give Informed Consent. Parent or guardian may give informed consent for minors.
  • Patient must be willing to and medically capable of undergoing the surgical operation.
  • Patients may not be receiving other investigational agent for the treatment of malignant brain tumor.
  • Patients must be at least 1 year old to participate in the study.

Exclusion:

  • Patients with diffuse subependymal or CSF disease.
  • Patients with tumors involving the cerebellum, or both hemispheres.
  • Patients with an active infection requiring treatment or having an unexplained febrile illness.
  • Patients who are known HIV positive or who are known positive for Hepatitis B or C virus
  • Patients who have received any form of radiation or chemotherapy within 4 weeks of protocol enrollment.
  • Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
  • Patients who have previously received systemic topotecan for their tumor
  • Patients less than 1 year of age
  • Patients who are not able to receive an MRI scan
  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: NCT00452959

Locations
United States, New York
Columbia University Department of Neurosurgery
New York City, New York, United States, 10032
Sponsors and Collaborators
Jeffrey N. Bruce
Herbert Irving Comprehensive Cancer Center
Investigators
Principal Investigator: Jeffrey N Bruce, M.D. Columbia University Department of Neurosurgery
  More Information

Publications:
B ruce, JN.,A. Falavigna, J.P. Johnson, J. Hall, B.d. Birch, J.T. Yoon, E.X.Wu, R.L. Fine, and A.T. Parsa, Intracerebral cylsis in a rat glioma model. Neurosurgery, 2000. 46(3): P. 683-691. Burris, H.A., 3rd, Topotecan: Incorporating It Into the Treatment of Solid Tumors. Oncologist, 1998. 3(1): p.1-3. Kaiser, M.G., A.T. Parsa, R.L. Fine, J.S. Hall, I. Chakrabarti, and J.N. Bruce, Tissue distribution and antitumor activity of topotecan delivered by intracerebral clysis in a rat glioma model. Neurosurgery, 2000. 47(6): p.1391-1399.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jeffrey N. Bruce, Edgar M. Housepian Professor of Neurological Surgery Research, Columbia University
ClinicalTrials.gov Identifier: NCT00452959     History of Changes
Obsolete Identifiers: NCT00324844
Other Study ID Numbers: AAAA4229 (I/II), R01CA089395
Study First Received: March 27, 2007
Last Updated: February 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Brain Tumors
Intracerebral Clysis
Topotecan
MRI

Additional relevant MeSH terms:
Oligodendroglioma
Glioblastoma
Brain Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014