CLINICAL TRIALS PROFILE FOR TEMOZOLOMIDE

505(b)(2) Clinical Trials for TEMOZOLOMIDE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT00876993 ↗	Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors	Completed	Brain Tumor Alliance	Phase 1	2008-09-01	Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
New Combination	NCT00876993 ↗	Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors	Completed	The V Foundation	Phase 1	2008-09-01	Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
New Combination	NCT00876993 ↗	Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors	Completed	V Foundation	Phase 1	2008-09-01	Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
New Combination	NCT00876993 ↗	Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors	Completed	Johns Hopkins All Children's Hospital	Phase 1	2008-09-01	Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
New Combination	NCT01051596 ↗	A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer	Completed	Abbott	Phase 2	2009-09-01	People with colorectal cancer that cannot be cured by surgery are being asked to participate in this study. The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with colorectal cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide, and will hopefully increase the killing of cancer cells, and decrease the tumors in the body. ABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in colorectal cancer. This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888 has on colorectal cancer. This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide for colorectal cancer.
New Combination	NCT01051596 ↗	A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer	Completed	Georgetown University	Phase 2	2009-09-01	People with colorectal cancer that cannot be cured by surgery are being asked to participate in this study. The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with colorectal cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide, and will hopefully increase the killing of cancer cells, and decrease the tumors in the body. ABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in colorectal cancer. This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888 has on colorectal cancer. This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide for colorectal cancer.

All Clinical Trials for TEMOZOLOMIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00003062 ↗	Temozolomide in Patients With Progressive or Recurrent Non-small Cell Lung Cancer	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 2	1997-07-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effect of temozolomide in patients with progressive or recurrent stage IV non-small cell lung cancer, with or without brain metastases, who have not been treated for metastatic disease with chemotherapy.
NCT00003176 ↗	Temozolomide and Carmustine in Treating Patients With Anaplastic Glioma	Completed	National Cancer Institute (NCI)	Phase 2	1998-03-25	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of temozolomide and carmustine in treating patients with anaplastic glioma.
NCT00003176 ↗	Temozolomide and Carmustine in Treating Patients With Anaplastic Glioma	Completed	North American Brain Tumor Consortium	Phase 2	1998-03-25	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of temozolomide and carmustine in treating patients with anaplastic glioma.
NCT00003176 ↗	Temozolomide and Carmustine in Treating Patients With Anaplastic Glioma	Completed	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Phase 2	1998-03-25	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of temozolomide and carmustine in treating patients with anaplastic glioma.
NCT00003273 ↗	Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor	Withdrawn	New York University School of Medicine	Phase 2	1997-11-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed brain tumor.
NCT00003273 ↗	Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor	Withdrawn	NYU Langone Health	Phase 2	1997-11-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of different regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed brain tumor.

Clinical Trial Conditions for TEMOZOLOMIDE

Condition Name

Condition Name for TEMOZOLOMIDE
Intervention	Trials
Glioblastoma	238
Glioblastoma Multiforme	138
Brain and Central Nervous System Tumors	89
Glioma	57

Condition MeSH

Condition MeSH for TEMOZOLOMIDE
Intervention	Trials
Glioblastoma	506
Glioma	212
Central Nervous System Neoplasms	113
Nervous System Neoplasms	109

Clinical Trial Locations for TEMOZOLOMIDE

Trials by Country

Trials by Country for TEMOZOLOMIDE
Location	Trials
Japan	81
Netherlands	62
Switzerland	58
Belgium	55
Austria	35

Trials by US State

Trials by US State for TEMOZOLOMIDE
Location	Trials
California	213
Texas	189
New York	180
North Carolina	163
Pennsylvania	161

Clinical Trial Progress for TEMOZOLOMIDE

Clinical Trial Phase

Clinical Trial Phase for TEMOZOLOMIDE
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	16
PHASE2	36

Clinical Trial Status

Clinical Trial Status for TEMOZOLOMIDE
Clinical Trial Phase	Trials
Completed	407
Recruiting	238
Not yet recruiting	113

Clinical Trial Sponsors for TEMOZOLOMIDE

Sponsor Name

Sponsor Name for TEMOZOLOMIDE
Sponsor	Trials
National Cancer Institute (NCI)	242
Schering-Plough	37
Merck Sharp & Dohme Corp.	36

Sponsor Type

Sponsor Type for TEMOZOLOMIDE
Sponsor	Trials
Other	1326
Industry	536
NIH	255

Temozolomide: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

Introduction

Temozolomide (TMZ), an oral alkylating chemotherapy agent, has established itself as a cornerstone in the treatment of glioblastoma multiforme (GBM), the most aggressive primary brain tumor. Since its FDA approval in 2005, TMZ's clinical application has expanded, complemented by ongoing research, evolving treatment protocols, and a dynamic market landscape. This report provides an in-depth review of recent clinical trial developments, comprehensive market analysis, and future projections for Temozolomide.

Clinical Trials Update

Current and Recent Clinical Developments

Over the past three years, clinical investigation into Temozolomide has concentrated on expanding its therapeutic indications, improving efficacy, reducing resistance, and optimizing combination regimens.

1. Trials Addressing Glioblastoma Multiforme

The National Cancer Institute (NCI) and various academic institutions have been testing novel combinations of TMZ with emerging therapeutic agents:

• Combination with Immunotherapies: Several phase I/II trials are examining TMZ in conjunction with immune checkpoint inhibitors such as pembrolizumab and nivolumab. For instance, a 2021 study (NCT04194215) investigated TMZ plus pembrolizumab in recurrent GBM, showing a modest improvement in progression-free survival (PFS). However, the overall survival (OS) benefit remains under evaluation.

• Targeting Resistance Mechanisms: Trials exploring TMZ with agents that inhibit DNA repair pathways, such as PARP inhibitors (e.g., niraparib), are ongoing (NCT04525516). These aim to counteract TMZ resistance caused by O6-methylguanine-DNA methyltransferase (MGMT) activity.

2. Extending Indications Beyond Glioblastoma

Research efforts have focused on leveraging TMZ’s efficacy in other malignancies:

• Anaplastic Astrocytoma: Trials (NCT02452050) are assessing TMZ's role in newly diagnosed high-grade gliomas beyond GBM.

• Metastatic Melanoma and Other Solid Tumors: Early-phase studies examine TMZ's utility in combination with targeted therapies in metastatic melanoma and soft tissue sarcomas, though clinical outcomes have been mixed.

3. Biomarker and Personalized Medicine Approaches

• Trials are investigating the predictive value of MGMT promoter methylation status to personalize TMZ therapy (NCT02781055). Results aim to optimize patient selection, thereby increasing response rates.

Ongoing Challenges in Clinical Trials

Despite advances, clinical trials reveal persistent challenges:

• Resistance Development: TMZ resistance remains prevalent, driven by MGMT activity and other resistance pathways.

• Limited Efficacy in Non-GBM Indications: Trials outside gliomas have yet to demonstrate significant benefits, highlighting a need for better patient stratification and combination strategies.

Market Analysis

Global Market Size and Segmentation

The Temozolomide market has experienced steady growth, driven primarily by its central role in glioblastoma therapy. In 2022, the global market was valued at approximately USD 750 million, with projections reaching USD 1.3 billion by 2030, exhibiting a compound annual growth rate (CAGR) of about 6.2%.

Key Market Segments:

• Geographical Distribution: North America dominates the market, accounting for over 50%, fueled by advanced healthcare infrastructure, high diagnosis rates, and reimbursement policies. Europe and Asia-Pacific follow, with emerging markets expecting significant growth due to increasing cancer incidences and expanding healthcare access.

• Formulation Type: Oral formulations dominate sales, owing to their convenience and compliance benefits. Injectable forms are largely obsolete but are still used in certain settings.

• Application: The primary application remains glioblastoma management, accounting for approximately 80% of sales, followed by other high-grade gliomas and experimental indications.

Competitive Landscape

Major pharmaceutical players include:

• Merck & Co. (brand: Temodal): The leading supplier globally, with extensive marketing channels and patent protections.

• Dr. Reddy's Laboratories: Offers generic formulations, increasing price competitiveness, especially in emerging markets.

• Other Generics Manufacturers: Numerous companies produce generic TMZ, enhancing accessibility but intensifying competition.

Market Drivers and Barriers

Drivers

• Unmet Medical Need in Glioblastoma: Limited effective therapies and a poor prognosis sustain high demand for TMZ.

• Growing Global Cancer Incidence: Increasing prevalence of gliomas and other tumors boosts market size.

• Adoption of Combination Therapies: Enhanced treatment regimens incorporating TMZ expand usage.

Barriers

• Patent Expiry and Generic Competition: Patent expiration has led to increased generics, pressuring prices.

• Side Effect Profile: Hematological toxicities may restrict usage or necessitate monitoring, limiting broader application.

• Regulatory and Reimbursement Challenges: Variability across markets can hinder sales expansion, especially in lower-income regions.

Future Market Projections

Market Growth Outlook

The Temozolomide market is poised for sustained growth, driven by innovations in combination therapy, biomarker-guided treatment, and expanding indications. Advanced formulations, such as sustained-release or novel delivery mechanisms, are anticipated to gain regulatory approval, further augmenting market penetration.

Innovation and Expansion Opportunities

• Personalized Medicine: Integration of MGMT methylation testing and other biomarkers will enhance efficacy and reduce unnecessary exposure.

• Next-Generation Derivatives: Development of TMZ analogs with improved pharmacokinetics and reduced toxicity could revolutionize treatment paradigms.

• Global Penetration: Lower-cost generic options and strategic partnerships will facilitate market expansion in emerging regions.

Risks and Uncertainties

• Clinical Efficacy Limitations: Failure to demonstrate significant benefits in new indications may restrict growth.

• Regulatory Hurdles: Stringent approval processes and safety concerns could delay new formulations.

• Competitive Dynamics: Emergence of novel therapeutic agents, especially immunotherapies and targeted treatments, may diminish TMZ's market share.

Conclusion

Temozolomide retains its status as a foundational therapy for glioblastoma, with ongoing clinical trials aiming to broaden its therapeutic utility and enhance outcomes. The marketplace is characterized by steady growth, influenced by increased cancer incidence, advancements in personalized medicine, and the proliferation of generic alternatives. Strategic innovations and tailored approaches are essential to sustain and expand TMZ’s market presence amid evolving competition and scientific landscapes.

Key Takeaways

• Clinical evolution focuses on combination therapies, resistance mitigation, and biomarker integration, with ongoing trials exploring new therapeutic synergies.

• Market size is projected to grow at a CAGR of approximately 6.2% through 2030, supported by high glioma prevalence and expanding indications.

• Generic competition has significantly shaped pricing strategies, with a focus on cost-effective formulations and global access.

• Future growth hinges on personalized treatment paradigms, next-generation analogs, and strategic market expansion in emerging economies.

• Challenges include managing toxicity, demonstrating incremental benefits beyond current standards, and navigating regulatory landscapes.

FAQs

1. What are the primary therapeutic uses of Temozolomide currently?
Temozolomide is primarily used for treating newly diagnosed and recurrent glioblastoma multiforme and anaplastic astrocytoma, especially in cases with MGMT promoter methylation, which predicts better responses.

2. Are there ongoing efforts to expand Temozolomide’s indications?
Yes. Clinical trials are investigating TMZ in combination with immunotherapies, targeted agents, and in other high-grade gliomas. Limited efficacy outside gliomas remains a challenge, but research persists.

3. How does MGMT methylation status influence TMZ therapy?
MGMT promoter methylation silences the DNA repair enzyme MGMT, reducing DNA repair and enhancing TMZ efficacy. Testing for MGMT methylation guides patient selection and personalized treatment strategies.

4. What are the main challenges facing the Temozolomide market?
Challenges include managing drug resistance, toxicity, decreasing profitability due to generic competition, and integrating new combination therapies that may overshadow TMZ.

5. What is the outlook for Temozolomide in emerging markets?
The outlook is promising, with growth driven by increasing cancer incidence, evolving healthcare infrastructure, and lower-cost generics enabling broader access, though regulatory and economic barriers remain.

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Sources

[1] Market research reports, 2022-2023.
[2] Clinical trial registries (clinicaltrials.gov).
[3] Peer-reviewed publications and pharmaceutical analyses.
[4] FDA and EMA regulatory updates.
[5] Industry reports on oncology therapeutics.