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A Phase 1 / 2 Dose Escalation Study of Locally-Administered OncoGel™ in Subjects With Recurrent Glioma
This study has been terminated.
( Sponsor business decision, not based on safety or efficacy data )
First Received: May 24, 2007   Last Updated: April 6, 2009   History of Changes
Sponsored by: Protherics
Information provided by: Protherics
ClinicalTrials.gov Identifier: NCT00479765
  Purpose

OncoGel™ is a new, experimental drug delivery system that allows the slow continuous release of paclitaxel (an approved intravenous anticancer drug), from a gel (ReGel™) over a long period of time. The gel will disappear in 4 to 6 weeks as it releases the paclitaxel.

The purpose of this study is to evaluate the safety and tolerability of OncoGel when placed into the tumor resection cavity in the brain following surgical removal of the tumor. Dose escalation is conducted by gradually increasing the amount of OncoGel placed in the resection cavity in small groups of patients, and watching the patients closely for side effects before moving to the next dose level. The study will also test whether OncoGel helps to prevent or delay the tumor from regrowing.


Condition Intervention Phase
Glioblastoma Multiforme
Brain Neoplasms
Drug: OncoGel (ReGel/Paclitaxel)
Phase I
Phase II

MedlinePlus related topics: Brain Cancer Cancer
Drug Information available for: Paclitaxel
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase 1 / 2 Dose Escalation Study of Locally-Administered OncoGel™ in Subjects With Recurrent Glioma

Further study details as provided by Protherics:

Primary Outcome Measures:
  • occurence of dose-limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • tumor response by MRI [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • individual survival [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • performance status (KPS and neurologic examination) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Occurrence of adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • CT Scan [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: March 2007
Estimated Study Completion Date: November 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
OncoGel administered into remaining cavity after surgical resection. Each dose cohort will receive a different volume of OncoGel
Drug: OncoGel (ReGel/Paclitaxel)
OncoGel administered into cavity after surgical resection of recurrent glioma. Each subject will receive one dose of OncoGel on the day of surgical resection.

Detailed Description:

This study is for patients with recurrent glioblastoma multiforme. Because most recurrences are in the area of the original resection, local delivery of a chemotherapeutic agent may prevent or delay additional recurrences. Paclitaxel has demonstrated activity against 9L glioma tumor lines, but has poor central nervous system penetration after intravenous administration. OncoGel is a new formulation of paclitaxel in a bioerodible gel that can be administered directly to the brain, thereby bypassing the blood-brain barrier.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 to less than 70 years of age
  • Radiological evidence on MRI of progressive recurrent malignant glioma that is unilateral, unifocal, supratentorial and of the minimum tumor volume as required per dose level assignment
  • Tumor must have a solid contrast enhancing component
  • Gross total resection >95% of the recurrence must be planned
  • Must have received prior conventional radiation therapy completed >4 weeks before Study Day 1 (ie, day of craniotomy and OncoGel administration)
  • Previous cytoreductive surgery or biopsy with pathologic diagnosis of glioblastoma multiforme
  • Diagnosis of glioma at the time of debulking surgery for recurrence (by frozen section or squash preparation)
  • Life expectancy > 2 months
  • KPS greater than or equal to 70
  • Using appropriate birth control, if female of child-bearing potential;
  • Able and willing to participate in the study by signing the informed consent document

Exclusion Criteria:

  • Contrast-enhancing tumor crossing the midline
  • Multifocal or non-contiguous tumor resulting in multiple resection cavities
  • Evidence of tumor dissemination (ependymal, leptomeningeal)
  • Tumors that result in a lobectomy or after resection leave an insufficient residual cavity to receive the expected OncoGel volume
  • Expected communication between the ventricle and resection cavity that cannot be repaired
  • Involvement of primary sensorimotor cortex in the dominant hemisphere or within 1.5 cm of the optic chiasm, either optic nerve or any other cranial nerve
  • Significantly increased intracranial pressure
  • Received any type of stereotactic radiosurgery or brachytherapy with the exception of a stereotactic radiosurgery boost as part of the initial radiation therapy
  • History of seizures refractory to two or more anticonvulsant medications co-administered at therapeutic levels
  • Impaired organ function as evidenced by clinically significant laboratory parameters including but not limited to the following: Hepatic Status:

Bilirubin >2.0 mg/dL; Aspartate transaminase (AST) >2.5 times the normal limit; Alanine aminotransferase (ALT) >2.5 times the normal limit.

Hematopoietic Status: Absolute neutrophil count (ANC) <1500mm3; Platelet count <100,000/mm3; Hemoglobin < 10 g/dL. Hemostatic: Prothrombin Time (PT) or INR above normal range; Partial Thromboplastin Time (PTT) above normal range; Bleeding Time outside normal range (if performed by hospital). Renal Status: Serum creatinine >2 mg/dL.

  • Contraindication to MRI
  • Receipt any chemotherapeutic agent within 28 days of Study Day 1 or nitrosourea within 6 weeks of Study Day 1
  • Received any intracerebral investigational agent
  • Receipt of another investigational drug or device within 28 days of the planned surgery
  • Known history of allergy to paclitaxel or any other component of OncoGel
  • Pregnant or lactating
  • Concurrent life-threatening disease
  • Any medical condition or other circumstance that, in the opinion of the Investigator, would make the subject unlikely or unable to successfully complete the study, or would interfere with analysis of study results
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479765

Locations
United States, Illinois
The University of Chicago Brain Tumor Center
Chicago, Illinois, United States, 60637
United States, Maryland
The Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Protherics
Investigators
Principal Investigator: Maciej S Lesniak, MD University of Chicago
  More Information

No publications provided

Responsible Party: Protherics ( Claire Daugherty, Clinical Project Manager )
Study ID Numbers: PR016-CLN-pro002, OGL-109
Study First Received: May 24, 2007
Last Updated: April 6, 2009
ClinicalTrials.gov Identifier: NCT00479765     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Protherics:
glioblastoma multiforme
recurrent
Phase 1
Phase 2
Phase I
Phase II
brain
cancer
paclitaxel
intracranial
tumor
local
chemotherapy
brain tumor
brain cancer
glioma
OncoGel

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Central Nervous System Diseases
Antimitotic Agents
Central Nervous System Neoplasms
Brain Diseases
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Paclitaxel
Neoplasms, Germ Cell and Embryonal
Tubulin Modulators
Neuroepithelioma
Glioma
Glioblastoma Multiforme
Antineoplastic Agents, Phytogenic
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Glioblastoma
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Brain Diseases
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Glioma
Nervous System Neoplasms
Neoplasms by Histologic Type
Astrocytoma
Nervous System Diseases
Mitosis Modulators
Central Nervous System Diseases
Antimitotic Agents
Pharmacologic Actions
Neuroectodermal Tumors
Brain Neoplasms
Neoplasms
Paclitaxel
Tubulin Modulators
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009