CLINICAL TRIALS PROFILE FOR GLEOSTINE

All Clinical Trials for Gleostine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Tactical Therapeutics, Inc.	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Annick Desjardins	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	AbbVie	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
NCT02724579 ↗	Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma	Recruiting	National Cancer Institute (NCI)	Phase 2	2017-10-02	This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.
NCT02724579 ↗	Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma	Recruiting	Children's Oncology Group	Phase 2	2017-10-02	This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Clinical Trial Conditions for Gleostine

Condition Name

Condition Name for Gleostine
Intervention	Trials
Glioblastoma	5
Glioblastoma Multiforme	3
Recurrent Anaplastic Astrocytoma	2
Anaplastic Astrocytoma	2

Condition MeSH

Condition MeSH for Gleostine
Intervention	Trials
Glioblastoma	9
Glioma	4
Gliosarcoma	2
Neoplasms	2

Clinical Trial Locations for Gleostine

Trials by Country

Trials by Country for Gleostine
Location	Trials
United States	145
Canada	16
Belgium	9
Germany	9
Australia	9

Trials by US State

Trials by US State for Gleostine
Location	Trials
California	7
Texas	6
New York	6
Massachusetts	6
North Carolina	6

Clinical Trial Progress for Gleostine

Clinical Trial Phase

Clinical Trial Phase for Gleostine
Clinical Trial Phase	Trials
Phase 3	2
Phase 2/Phase 3	1
Phase 2	6

Clinical Trial Status

Clinical Trial Status for Gleostine
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	4
Completed	2

Clinical Trial Sponsors for Gleostine

Sponsor Name

Sponsor Name for Gleostine
Sponsor	Trials
National Cancer Institute (NCI)	3
Monteris Medical	1
The University of Texas Health Science Center at San Antonio	1

Sponsor Type

Sponsor Type for Gleostine
Sponsor	Trials
Other	11
Industry	10
NIH	3

Gleostine (Lomustine) Clinical Trials and Market Outlook

Last updated: February 19, 2026

Gleostine (lomustine) exhibits a persistent but evolving role in oncology, primarily for brain tumors. Recent clinical trial activity focuses on combination therapies and recalibrating its therapeutic index, while the market navigates generic competition and the emergence of targeted agents.

What is the Current Status of Gleostine's Regulatory Approvals?

Gleostine, a nitrosourea alkylating agent, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of brain tumors, including glioblastoma multiforme and anaplastic astrocytoma, and also for Hodgkin's disease, in combination with other agents. Its initial approval for brain tumors was in 1976. In Europe, it also holds marketing authorization for similar indications.

What Are the Key Clinical Trials Involving Gleostine?

Clinical trial enrollment for Gleostine has shifted from monotherapy studies to investigating its efficacy in combination with other agents, particularly novel therapies. The focus is on identifying synergistic effects and mitigating toxicity.

• Combination Therapy in Glioblastoma Multiforme (GBM):

  • A Phase 2 trial (NCT03328983) investigated the combination of lomustine, temozolomide (TMZ), and radiation therapy in newly diagnosed GBM patients. This study aimed to evaluate overall survival (OS) and progression-free survival (PFS).
  • Another Phase 2 study (NCT02900943) is evaluating lomustine and bevacizumab in recurrent GBM. The primary endpoint is objective response rate (ORR).
  • A Phase 3 trial (NCT02697134) previously assessed lomustine, vincristine, and procarbazine alongside radiotherapy in newly diagnosed GBM. While not exclusively Gleostine, it highlights the enduring interest in nitrosourea-based regimens.

• Second-Line and Recurrent Brain Tumors:

  • Numerous trials explore lomustine as a salvage therapy for patients who have progressed on standard treatments, often in combination with agents like everolimus or other targeted therapies. Data from such trials are often presented at major oncology conferences.

• Pediatric Brain Tumors:

  • While less common, some early-phase trials have explored lomustine in pediatric brain tumor contexts, particularly for recurrent or refractory disease.

How Does Gleostine's Pharmacological Profile Inform its Clinical Use?

Lomustine is orally administered, offering a significant convenience advantage. Its lipophilicity allows it to cross the blood-brain barrier effectively, making it a cornerstone for treating primary and metastatic brain tumors.

• Mechanism of Action: Lomustine is a potent alkylating agent that interferes with DNA and RNA synthesis and function. It forms DNA cross-links, leading to cell cycle arrest and apoptosis.
• Pharmacokinetics:
  • Absorption: Oral bioavailability is approximately 90%.
  • Distribution: Widely distributed throughout the body, including the central nervous system.
  • Metabolism: Extensively metabolized in the liver.
  • Elimination: Excreted primarily in urine.
• Toxicity Profile: The primary dose-limiting toxicities are myelosuppression (thrombocytopenia, leukopenia) and gastrointestinal distress (nausea, vomiting). Delayed and cumulative myelosuppression is a characteristic feature, requiring careful monitoring. Pulmonary toxicity and potential for secondary malignancies are also concerns.

What is the Current Market Landscape for Gleostine?

The Gleostine market is characterized by its established use in specific indications, generic availability, and increasing competition from newer, targeted therapies.

Key Market Dynamics:

• Generic Competition: Gleostine is available as a generic product, significantly impacting pricing and market share for branded versions. The originator product, Gleostine, faces competition from multiple generic manufacturers.
• Established Niche: Despite newer agents, lomustine remains a standard of care in certain brain tumor treatment paradigms, particularly as a salvage therapy or in specific patient populations where cost-effectiveness is a consideration.
• Emergence of Targeted Therapies: The oncology market is increasingly driven by targeted therapies and immunotherapies. For brain tumors, agents targeting specific molecular pathways are gaining traction, potentially reducing reliance on cytotoxic chemotherapy like lomustine for certain patient subgroups.
• Combination Therapy Research: Ongoing clinical trials investigating lomustine in combination with novel agents represent efforts to revitalize its therapeutic utility and potentially create new market opportunities, though these are often in early stages.
• Geographic Variations: Market penetration and pricing vary significantly by region, influenced by regulatory frameworks, healthcare system structures, and the availability of competing treatments.

What is the Projected Market Size and Growth for Gleostine?

Forecasting the precise market size for Gleostine is challenging due to its generic status and integration into multi-drug regimens. However, the overall market for brain tumor therapeutics continues to grow.

• Declining Monotherapy Share: The market share of lomustine as a standalone therapy is likely to continue a slow decline as more effective targeted agents become available for first-line treatment.
• Sustained Use in Salvage Settings: Its role in salvage chemotherapy for recurrent or refractory brain tumors is expected to persist due to its established efficacy and oral administration. This segment will likely provide a stable, albeit not growing, revenue stream.
• Impact of Combination Therapies: If clinical trials demonstrate significant benefits for lomustine in combination with emerging drugs, it could lead to a resurgence in its use and a corresponding increase in market demand, though this remains speculative.
• Global Market Value for Brain Tumor Drugs: The global market for brain tumor drugs was valued at approximately USD 2.8 billion in 2022 and is projected to grow at a compound annual growth rate (CAGR) of around 5.5% to reach an estimated USD 4.5 billion by 2030. [1] Gleostine's direct contribution to this figure will be a subset, influenced by its specific indications and competitive positioning.
• Generic Market Dynamics: The generic market for lomustine is highly fragmented and price-sensitive. Growth in this segment will be driven by volume rather than price increases.

Competitive Landscape:

• Temozolomide (TMZ): The most significant competitor and often used in conjunction with or as an alternative to lomustine for GBM.
• Targeted Therapies: Bevacizumab, EGFR inhibitors, and IDH inhibitors are increasingly important for specific molecular subtypes of brain tumors.
• Immunotherapies: While less established in primary brain tumors, ongoing research is exploring their role.
• Other Cytotoxic Agents: Carmustine (BCNU) and other chemotherapy drugs are also part of the treatment landscape.

What are the Key Challenges and Opportunities for Gleostine?

Challenges:

• Toxicity Management: Myelosuppression and other adverse effects remain a significant challenge, requiring close patient monitoring and dose adjustments.
• Resistance Mechanisms: Tumors can develop resistance to alkylating agents, limiting long-term efficacy.
• Competition from Novel Agents: The rapid development of targeted therapies and immunotherapies for brain tumors poses a substantial competitive threat.
• Limited New Drug Development: Investment in novel clinical trials for lomustine monotherapy is low due to its established profile and the focus on newer drug classes.

Opportunities:

• Repurposing and Combination Strategies: Identifying novel combination therapies with synergistic effects and improved safety profiles presents the most significant opportunity.
• Cost-Effectiveness: As a generic drug, lomustine offers a cost-effective option, particularly in resource-constrained healthcare systems or for patients who cannot tolerate more expensive targeted agents.
• Long-Term Salvage Therapy: Its established role in treating recurrent or refractory disease provides a sustained market niche.
• Biomarker-Driven Treatment: Further research into biomarkers that predict response or resistance to lomustine could refine its use and identify patient populations who would benefit most.

Key Takeaways

Gleostine (lomustine) remains a relevant agent in brain tumor treatment, primarily for its ability to cross the blood-brain barrier and its established efficacy as a salvage therapy. Clinical trials are focused on combination regimens to enhance efficacy and manage toxicity. The market is characterized by generic competition and the growing influence of targeted therapies. While its role as a monotherapy may diminish, its utility in salvage settings and potential for synergistic combinations offer continued, albeit evolving, market presence. The overall market for brain tumor therapeutics is expanding, providing a backdrop for lomustine's performance.

FAQs

1. What specific types of brain tumors is Gleostine primarily used for? Gleostine is primarily approved for and used in the treatment of brain tumors, including glioblastoma multiforme and anaplastic astrocytoma. It is also indicated for Hodgkin's disease in combination therapy.

2. Is Gleostine still considered a first-line treatment for newly diagnosed glioblastoma? For newly diagnosed glioblastoma, temozolomide (TMZ) is typically the first-line chemotherapy agent, often used concurrently with radiation therapy. Gleostine is more commonly employed as a salvage therapy in recurrent or refractory settings, or in specific combination regimens.

3. What are the main side effects associated with Gleostine treatment? The primary dose-limiting toxicities of Gleostine are myelosuppression (low blood cell counts, including platelets and white blood cells) and gastrointestinal issues such as nausea and vomiting. Delayed and cumulative bone marrow suppression is a characteristic concern.

4. How does the oral administration of Gleostine compare to intravenous chemotherapy for brain tumors? Oral administration offers significant convenience for patients and healthcare providers, eliminating the need for intravenous infusions. This is particularly advantageous for long-term treatment courses. Its lipophilicity also ensures good penetration into the central nervous system.

5. What is the outlook for Gleostine in the context of emerging targeted therapies and immunotherapies for brain tumors? While newer targeted agents and immunotherapies are gaining prominence, Gleostine is expected to retain its role in salvage chemotherapy and potentially in specific combination regimens where it demonstrates synergistic benefits. Its cost-effectiveness as a generic drug may also ensure its continued use.

Citations

[1] Grand View Research. (2023). Brain Tumor Drugs Market Size, Share & Trends Analysis Report By Drug Type (Chemotherapy, Targeted Therapy, Immunotherapy), By Application (Glioblastoma, Meningioma, Primary CNS Lymphoma, Others), By End-Use (Hospitals, Clinics, Research Institutes), By Region (North America, Europe, Asia Pacific, Latin America, Middle East & Africa), And Segment Forecasts, 2023 – 2030. Retrieved from https://www.grandviewresearch.com/industry-analysis/brain-tumor-drugs-market