Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas

2014-07-24 14:18:53 | BioPortfolio



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


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.

Study Design

Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment




Temodar, O6-BG, and Irinotecan


Duke University Health System
North Carolina
United States




Duke University

Results (where available)

View Results


Published on BioPortfolio: 2014-07-24T14:18:53-0400

Clinical Trials [1014 Associated Clinical Trials listed on BioPortfolio]

Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma

This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a sta...

Ph. II Treatment of Adults w Primary Malignant Glioma w Irinotecan + Temozolomide

Objective: To determine activity of combo of Irinotecan + Temozolomide To further characterize any toxicity associated w combo of Irinotecan + Temozolomide

Phase II Study of Temozolomide in Newly Diagnosed Glioblastoma

A single arm Phase 2 trial with the study drug temozolomide (temodar) for newly diagnosed glioblastoma in elderly patients (defined as greater than or equal to 70 years old). Following sur...

Sarasar and Temodar for Glioblastoma Multiforme Patients

Primary Objectives: - To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule. - ...

Dietary Methionine Restriction Plus Temozolomide for Recurrent GBM

Objectives: 1. To determine the safety, tolerability and efficacy of dietary methionine restriction for 7 days alternating with Temodar® (Temozolomide) given once a day for seven ...

PubMed Articles [436 Associated PubMed Articles listed on BioPortfolio]

Xiao-Chai-Hu-Tang (XCHT) Intervening Irinotecan's Disposition: The Potential of XCHT in Alleviating Irinotecan-Induced Diarrhea.

Diarrhea is a severe side effect of irinotecan, a pro-drug of SN-38 used for the treatment of many types of cancers. Pre-clinical and clinical studies showed that decreasing the colonic exposure of SN...

Baseline T1 hyperintense and diffusion-restricted lesions are not linked to prolonged survival in bevacizumab-treated glioblastoma patients of the GLARIUS trial.

The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase promoter non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or stan...

A novel mechanism of irinotecan targeting MDM2 and Bcl-xL.

Irinotecan is a strong anticancer drug whose mechanism of action has been reported only for the inhibition of DNA topoisomerase I (Topo I) through its active metabolite SN-38. In this study, we presen...

Conjugation Of Dasatinib With MHI-148 Has A Significant Advan-tageous Effect In Viability Assays For Glioblastoma Cells.

We hypothesized conjugation of the near-IR dye MHI-148 to dasatinib might produce a potential theranostic for glioblastoma. In fact, the conjugate bound the kinases Src and Lyn, and inhibits the viabi...

Development of a Microfluidic Culture Paradigm for Ex Vivo Maintenance of Human Glioblastoma Tissue: A New Glioblastoma Model?

One way to overcome the genetic and molecular variations within glioblastoma is to treat each tumour on an individual basis. To facilitate this, we have developed a microfluidic culture paradigm that ...

Medical and Biotech [MESH] Definitions

Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)

A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.

A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.

Intracranial tumors originating in the region of the brain inferior to the tentorium cerebelli, which contains the cerebellum, fourth ventricle, cerebellopontine angle, brain stem, and related structures. Primary tumors of this region are more frequent in children, and may present with ATAXIA; CRANIAL NERVE DISEASES; vomiting; HEADACHE; HYDROCEPHALUS; or other signs of neurologic dysfunction. Relatively frequent histologic subtypes include TERATOMA; MEDULLOBLASTOMA; GLIOBLASTOMA; ASTROCYTOMA; EPENDYMOMA; CRANIOPHARYNGIOMA; and choroid plexus papilloma (PAPILLOMA, CHOROID PLEXUS).

More From BioPortfolio on "Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas"

Quick Search

Relevant Topic

Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Searches Linking to this Trial