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Project Details
  • Title: Preclinical Studies on Convection Enhanced Delivery of Carbolatin in Comination with Photon Irradiation for the Treatment of Gliomas
  • Date Proposed: 07/27/2008
  • Amount Requested: $45,000.00
  • Amount we Paid: $45,000.00
  • Paid Date: 03/20/2009
  • Stauts: Completed
  • Research name: Rolf F. Barth, M.D.
  • Hospital: Ohio State University Medical Center
  • Grey Ribbon Crusade Participants:
    • Musella Foundation For Brain Tumor Research & Information, Inc
    • Have A Chance Inc.
    • Unlocking Brain Tumors, Inc
    • The Brad Kaminsky Foundation for Brain Tumor Research
  • Simple Description: Phase I study of convection enhanced delivery of carboplatin in patients with recurrent malignant glioma. Study Agent: Carboplatin Objectives: Primary objective: Establish the maximum tolerated dose and define the toxicity profile of carboplatin delivered intracerebrally via convection enhanced delivery Secondary objectives: Examine the efficacy as defined by six-month progression free survival and median progression free survival and to evaluate the radiographic response rate. Study Design: Phase I dose escalation study Population: Patients, aged 18 to 70, with grade III astrocytoma, oligodendroglioma, or oligastrocytoma or IV astrocytoma at first or second recurrence are eligible to enroll in this protocol. Subjects are required to have radiographic confirmation of disease progression and a Karnofsky Performance Status of at least 60. Eligible patients must be at least 6 weeks out from last dose of nitrosoureas, bevacizumab and other antiangiogenic therapies, 8 weeks out from completion of radiotherapy (fractionated or stereotactic), and 4 weeks out from last dose of other cytotoxic chemotherapies. Patient cannot be receiving other investigational agents and must be on a stable dose of dexamethasone for ?1 week prior to baseline MRI. Treatment Schedule: Patients will stereotactically undergo frozen biopsy confirmation of recurrent malignant glioma vs. other diagnosis (radionecrosis). At the same sitting, they will have stereotactic insertion of up to 4 catheters into the area of tumor. Infusions will commence after Ct or MRI confirmation of placement for up to 3 days. Assessments: Study patients will be evaluated clinically monthly for the first six months and every two months thereafter. Evaluation will include full neurological and general examination, mini-mental status examination, and Karnofsky Performance Status. MRI, performed every 2 months, will be evaluated per McDonald criteria. Additional ancillary imaging will be used when imaging changes are suggestive of a treatment related effect. Toxicity will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Proposed trial: Patients would be infused at 0.5uL/hour. Proposed starting dose is 10 µug. Dosage escalation proceeded in subsequent cohorts (20µg, 33 µg, 50µg, 70µg) until the MTD or the maximum proposed dose of 100µg is reached. Cohorts of three evaluable patients will be used, and dose escalation will be performed if zero of three patients have a dose-limiting toxicity (DLT). An additional three patients were enrolled if one of three patients develop a DLT. DLTs are defined, in the presence of supportive care, as any Grade 3 or 4 toxicity that is possibly, probably, or definitely related to the study drug. The maximum tolerated infusate dosage is defined as the dose level below that causing DLT in two to six patients. In this study, we will evaluate the efficacy of direct delivery of the drug carboplatin into the brains of rats bearing malignant brain tumors. We will use a special technique employing small pumps to increase the distribution of the drug. Twenty-four hours after administering the anti-cancer drug, carboplatin, the animals will begin to receive the first of 3 daily X-ray treatments. We already have shown that this combination of delivery of drug to the brain and synchrotron X-irradiation can cure up to 60% of rats bearing this malignant brain tumor, which are the best survival data ever obtained by anyone working with this brain tumor model. The purpose of these studies will be to obtain animal data using a very standard type of X-irradiation that will help to better define the efficacy of this treatment, but also the toxic effects that it may have on normal brain. The information obtained from these studies will help us to develop a clinical trial to evaluate this combination of chemotherapy and radiation therapy in patients that have malignant brain tumors.
  • Final Report: Click HERE for final report!