Temozolomide

Generic Name: Temozolomide

Brand Names: Temodar, Temomedac, Temodal, Temozolomide Sun, Temozolomide Accord, Temozolomide Teva

Drug Type: Small Molecule

Chemical Formula: C_₆H_₆N_₆O_₂

CAS Number: 85622-93-1

Unique Ingredient Identifier: YF1K15M17Y

Background: Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time. Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration. Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual apoptosis. Temozomolide as an adjunct to radiotherapy followed by maintenance dosing remains the standard of care for both Glioblastoma and refractory anaplastic astrocytoma.

Temozolomide was granted FDA approval on August 11, 1999, as an oral capsule and subsequently on February 27, 2009, as an intravenous injection. It is currently marketed under the trademark TEMODAR® by Merck.

Indication: Temozolomide is indicated in adult patients for the treatment of newly diagnosed glioblastoma concomitantly with radiotherapy and for use as maintenance treatment thereafter. It is also indicated for the treatment of refractory anaplastic astrocytoma in adult patients or adjuvant therapy for adults with newly diagnosed anaplastic astrocytoma.

Associated Conditions: Advanced Melanoma, High Grade Glioma: Glioblastoma (GBM), Primary Central Nervous System Lymphoma, Refractory Ewing Sarcoma, Refractory Neuroblastoma, Soft Tissue Sarcoma, Advanced Neuroendocrine tumor, Newly diagnosed Anaplastic Astrocytoma (AA), Refractory Anaplastic astrocytoma, Refractory, advanced Mycosis fungoides, Refractory, advanced Sezary Syndrome

Associated Therapies: -

Clinical Trials

Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma

Phase 1

Terminated

Conditions: Neuroblastoma

Interventions: Drug: TPI 287
Drug: Temozolomide
Drug: Irinotecan

First Posted Date: 2012-01-06

Last Posted Date: 2024-08-06

Lead Sponsor: Giselle Sholler

Target Recruit Count: 14

Registration Number: NCT01505608

Locations: 🇺🇸
Rady Children's Hospital, San Diego, California, United States
🇺🇸
Helen DeVos Children's Hospital, Grand Rapids, Michigan, United States
🇺🇸
Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States

and more 5 locations

Phase III Trial of Primary Radio- or Chemotherapy in Malignant Astrocytoma of the Elderly

Phase 3

Completed

Conditions: Glioblastoma
Anaplastic Astrocytoma

Interventions: Radiation: Radiotherapy of the partial brain.
Drug: Temozolomide

First Posted Date: 2011-12-30

Last Posted Date: 2011-12-30

Lead Sponsor: Heidelberg University

Target Recruit Count: 412

Registration Number: NCT01502241

Locations: 🇩🇪
University of Heidelberg, Mannheim, Germany
🇩🇪
Charite Berlin, Berlin, Germany
🇩🇪
University of Bochum, Bochum, Germany

and more 19 locations

Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma

Phase 3

Completed

Conditions: Glioblastoma
Small Cell Glioblastoma
Giant Cell Glioblastoma
Gliosarcoma
Glioblastoma With Oligodendroglial Component

Interventions: Drug: Rindopepimut (CDX-110) with GM-CSF
Drug: Temozolomide
Drug: KLH

First Posted Date: 2011-11-29

Last Posted Date: 2018-01-16

Lead Sponsor: Celldex Therapeutics

Target Recruit Count: 745

Registration Number: NCT01480479

Locations: 🇺🇸
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, United States
🇺🇸
University of Chicago, Chicago, Illinois, United States
🇺🇸
Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

and more 220 locations

Mibefradil Dihydrochloride and Temozolomide in Treating Patients With Recurrent Glioma

Phase 1

Completed

Conditions: Brain and Central Nervous System Tumors

Interventions: Drug: temozolomide
Other: 3'-deoxy-3'-[18F]fluorothymidine
Other: pharmacological study
Drug: Mibefradil

First Posted Date: 2011-11-28

Last Posted Date: 2019-05-22

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Target Recruit Count: 28

Registration Number: NCT01480050

Locations: 🇺🇸
UAB Comprehensive Cancer Center, Birmingham, Alabama, United States
🇺🇸
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina, United States
🇺🇸
Henry Ford Hospital, Detroit, Michigan, United States

and more 4 locations

Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas

Phase 2

Terminated

Conditions: Adult Anaplastic Ependymoma
Adult Giant Cell Glioblastoma
Adult Anaplastic Oligodendroglioma
Adult Anaplastic Astrocytoma
Adult Glioblastoma

Interventions: Drug: Temozolomide
Radiation: hypofractionated radiation therapy
Biological: bevacizumab
Other: questionnaire administration

First Posted Date: 2011-11-23

Last Posted Date: 2020-03-12

Lead Sponsor: Northwestern University

Target Recruit Count: 54

Registration Number: NCT01478321

Locations: 🇺🇸
Northwestern Lake Forest Hospital, Lake Forest, Illinois, United States
🇺🇸
Edward Cancer Center, Naperville, Illinois, United States
🇺🇸
Northwestern University, Chicago, Illinois, United States

and more 2 locations

Multimodal Molecular Targeted Therapy to Treat Relapsed or Refractory High-risk Neuroblastoma

Phase 2

Completed

Conditions: Neuroblastoma Recurrent

Interventions: Drug: Temozolomide
Drug: Dasatinib
Drug: Irinotecan
Drug: Rapamycin

First Posted Date: 2011-11-09

Last Posted Date: 2020-10-06

Lead Sponsor: University of Regensburg

Target Recruit Count: 130

Registration Number: NCT01467986

Locations: 🇩🇪
University Hospital Regensburg, Department of Pediatric Hematology and Oncology, Regensburg, Germany

Low Dose Radiation Therapy for Glioblastoma Multiforme

Phase 2

Completed

Conditions: High Grade Glioma

Interventions: Radiation: Low Dose Fractionated Radiation Therapy (LDFRT)
Drug: Temozolomide

First Posted Date: 2011-11-08

Last Posted Date: 2023-07-03

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Target Recruit Count: 31

Registration Number: NCT01466686

Locations: 🇺🇸
Sibley Memorial Hospital, Washington, District of Columbia, United States
🇺🇸
Suburban Hospital, Bethesda, Maryland, United States
🇺🇸
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States

Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

Phase 1

Completed

Conditions: Pancreatic Alpha Cell Carcinoma
Pancreatic Beta Islet Cell Carcinoma
Pancreatic Delta Cell Carcinoma
Pancreatic G-cell Carcinoma
Recurrent Islet Cell Carcinoma

Interventions: Drug: temozolomide
Drug: pazopanib hydrochloride

First Posted Date: 2011-11-06

Last Posted Date: 2021-08-05

Lead Sponsor: Northwestern University

Target Recruit Count: 29

Registration Number: NCT01465659

Locations: 🇺🇸
University of Michigan, Ann Arbor, Michigan, United States
🇺🇸
Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States
🇺🇸
Vanderbilt University, Nashville, Tennessee, United States

and more 2 locations