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Sponsors and Collaborators: |
Duke University AOI Pharma, Inc. Pharmacia |
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Information provided by: | Duke University |
ClinicalTrials.gov Identifier: | NCT00612638 |
Objectives:
To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar plus O6-BG To observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar + O6-BG
Condition | Intervention | Phase |
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Glioblastoma Gliosarcoma |
Drug: Temodar, O6-BG, and Irinotecan |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study |
Official Title: | Phase I Trail of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) Plus Irinotecan (CPT-11) (NSC 616348) in the Treatment of Patients With Recurrent / Progressive Cerebral Anaplastic Gliomas |
Estimated Enrollment: | 96 |
Study Start Date: | January 2005 |
Study Completion Date: | July 2008 |
Primary Completion Date: | January 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Pts receiving Dilantin, Tegretol or Phenobarbital
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Drug: Temodar, O6-BG, and Irinotecan
2 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 & 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle. |
2: Experimental
Pts on anti-convulsants other than Dilantin, Tegretol / Phenobarbital / pts not on any anti-convulsants
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Drug: Temodar, O6-BG, and Irinotecan
2 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 & 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle. |
Objectives of study: to determine maximum tolerated dose of CPT-11 when administered following Temodar + O6-benzylguanine (O6-BG); to characterize any toxicity associated w combo of CPT-11 + Temodar + O6-BG; to observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar plus
O6-BG. Pts have histologically confirmed diagnosis of recurrent primary malignant glioma. 2 separate strata accrued independently of each other:
Stratum 1-pts receiving Dilantin, Tegretol/phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. Each strata will be treated & escalated independent of each other.
Pre-chemo, O6-BG administered intravenously at 120 mg/m2, over 1hr, prior to administration of Temodar on day 1 of 21-day cycle. Post-chemo, O6-BG administered intravenously at 30 mg/m2/day, over 48hrs, immediately after completion of the CPT-11 infusion on day 1 of 21-day cycle. Temodar administered orally at 355 mg/m2, in fasting state, within 60 minutes of the end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3 weeks following dose of Temozolomide from previous cycle. CPT-11 will be administered intravenously in fasting state over 90min. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60 mg/m2 for stratum 1 & 40 mg/m2 for stratum 2. Treatment cycles may be repeated every 3 wks following dose of CPT-11 from previous cycle. Major toxicities associated w CPT- 11 are myelosuppression & diarrhea. Temozolomide has been well tolerated by both adults & children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea & vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, & hepatotoxicity. Hypersensitivity reactions have not yet been noted w Temozolomide. As is case w many anti-cancer drugs, Temozolomide may be carcinogenic. O6-BG toxicities include transient lymphopenia has been seen w O6-BG as single agent. O6-BG in combo w other agents could cause exacerbation of any adverse event currently known to be caused by other agent,/ combo may result in events never previously associated w either agent. Animal studies indicated that agitation, lethargy, convulsions, nausea, vomiting, rapid heart rate, elevated liver functions, leukopenia, lymphopenia could be seen.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, North Carolina | |
Duke University Health System | |
Durham, North Carolina, United States, 27710 |
Principal Investigator: | David A. Reardon, MD | Duke University Health System |
Responsible Party: | Duke University Health System ( David A. Reardon, MD ) |
Study ID Numbers: | 4883/00007681 |
Study First Received: | January 29, 2008 |
Last Updated: | January 22, 2009 |
ClinicalTrials.gov Identifier: | NCT00612638 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Temodar Temozolomide O6-Benzylguanine O6-BG NSC 637037 |
Irinotecan CPT-11 Recurrent cerebral anaplastic glioma Progressive cerebral anaplastic glioma Malignant glioma |
Glioblastoma Phenobarbital Astrocytoma Irinotecan Temozolomide Recurrence Phenytoin Neuroectodermal Tumors Carbamazepine Neoplasms, Germ Cell and Embryonal |
Neuroepithelioma O(6)-benzylguanine Antineoplastic Agents, Alkylating Glioma Gliosarcoma Antineoplastic Agents, Phytogenic Alkylating Agents Anticonvulsants Neoplasms, Glandular and Epithelial |
Glioblastoma Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Astrocytoma Antineoplastic Agents Irinotecan Neoplasms, Nerve Tissue Enzyme Inhibitors Temozolomide Pharmacologic Actions Neuroectodermal Tumors |
Neoplasms Therapeutic Uses Neoplasms, Germ Cell and Embryonal O(6)-benzylguanine Antineoplastic Agents, Alkylating Glioma Gliosarcoma Neoplasms, Neuroepithelial Antineoplastic Agents, Phytogenic Alkylating Agents Neoplasms, Glandular and Epithelial |