Berubicin for Glioblastoma

Recruiting at 65 trial locations

Overseen By Zena Muzyczenko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CNS Pharmaceuticals, Inc.

Must not be taking: Bevacizumab, Lomustine, others

Disqualifiers: Heart disease, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

210 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have recovered from the side effects of previous treatments and meet certain health criteria, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Berubicin for treating glioblastoma?

Research shows that lomustine, a component of the treatment, has been used in combination with other drugs like temozolomide and radiotherapy to treat glioblastoma, suggesting potential benefits. However, the effectiveness of lomustine alone or in combination with other drugs like Berubicin specifically for glioblastoma is not clearly established in the provided studies. ^{1 2 3 4 5}

Is Berubicin (also known as Lomustine or CCNU) safe for humans?

Lomustine (CCNU), which is related to Berubicin, can cause serious side effects like lung problems and blood-related issues such as low white blood cell counts and low platelets. These side effects have been observed in studies involving patients with brain tumors. ^{2 6 7 8 9}

What makes the drug Berubicin for Glioblastoma unique compared to other treatments?

Berubicin is unique because it is designed to cross the blood-brain barrier, which is a protective shield around the brain that many drugs cannot penetrate, potentially making it more effective for treating brain tumors like glioblastoma. Lomustine, often used in combination with other drugs, is known for its ability to treat recurrent glioblastoma, but it can have serious side effects like lung toxicity. ^{2 6 10 11 12}

What is the purpose of this trial?

This is an open-label, multicenter, randomized, parallel, 2-arm, efficacy and safety study. Patients with GBM after failure of standard first line therapy will be randomized in a 2:1 ratio to receive berubicin or lomustine for the evaluation of OS. Additional endpoints will include response and progression outcomes evaluated by a blinded central reviewer for each patient according to RANO criteria. A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months. This review will include additional evaluation of safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.

Research Team

Sandra Silberman, MD, PhD

Principal Investigator

CNS Pharmaceuticals, Inc.

Eligibility Criteria

Adults with recurrent Glioblastoma Multiforme (GBM) who've had standard treatment can join. They must have recovered from previous treatments, be eligible for chemotherapy, and not have used certain drugs like bevacizumab or lomustine before. Women of childbearing age need to use contraception.

Inclusion Criteria

My brain tumor has not spread to the spinal cord, brain linings, or ventricles.

Women of childbearing potential must agree to practice a highly effective method of contraception beginning at least 28 days before the start of treatment until at least 6.25 months after the last dose of study drug. Male study patients and their female sexual partners of childbearing potential must agree to practice a highly effective method of contraception starting from the time of informed consent until at least 3.5 months (no less than 104 days) after the last dose of study drug.

Written informed consent from the patient or their legally authorized representative (LAR) prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.

Exclusion Criteria

You are a woman who is currently breastfeeding.

My blood pressure is not higher than 150/100 mmHg.

I have heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive berubicin intravenously infused at a dose of 7.1 mg/m2 as a 2-hour IV infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days). Lomustine is administered as per institutional guidelines.

21 days per cycle

Interim Analysis

A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations including overall survival and progression-free survival.

4 years

Treatment Details

Interventions

• Berubicin
• Lomustine

Trial Overview The study compares the effectiveness and safety of Berubicin versus Lomustine in treating GBM after first-line therapy fails. Patients are randomly assigned to either drug in a 2:1 ratio, focusing on overall survival rates and response to treatment.

Participant Groups

Group I: Berubicin Experimental Treatment 1 Intervention

Berubicin intravenously infused will be administered at a dose of 7.1 mg/m2 as free base as a 2 hour intravenous (IV) infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days) Each treatment cycle is 21 days. Subjects will be allowed to continue on treatment at the discretion of the Investigator if there is no evidence of disease progression and the subject is not experiencing unacceptable toxicity as well as if both the subject and Investigator agree that further therapy is in the subject's best interest.

Group II: Lomustine (CCNU, CeeNU®, or Gleostine®) capsules Active Control 1 Intervention

Lomustine (CCNU, CeeNU®, or Gleostine®) capsules will be administered at the institutionally-approved dose and regimen or per the full prescribing information/summary of product characteristics.

Who Is Running the Clinical Trial?

CNS Pharmaceuticals, Inc.

Lead Sponsor

Trials

1

Recruited

210+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

In a study of 39 patients with newly diagnosed glioblastoma, the combination of radiotherapy and chemotherapy (lomustine and temozolomide) resulted in a median overall survival of 23.1 months, with 47.4% of patients surviving for 2 years and 18.5% for 4 years.

Patients receiving an intensified dose of chemotherapy showed significantly higher survival rates compared to those on standard doses, with some patients in the intensified group surviving over 56 months, although this came with a higher risk of severe hematotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. Glas, M., Happold, C., Rieger, J., et al.[2022]

In a study involving 97 patients with malignant gliomas, temozolomide (TMZ) demonstrated a significantly higher response rate (35.71%) compared to lomustine (CCNU) (9.09%), indicating its greater efficacy in treating these aggressive brain tumors.

TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy option for patients with refractory malignant brain gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. Qian, ZZ., Wang, HQ., Liu, XM., et al.[2018]

In a study of 166 brain tumor patients treated with CCNU, there was no significant overall change in lung function, but a notable decrease in vital capacity was observed in patients with prior lung diseases and smokers.

The results suggest that lung function monitoring during CCNU treatment should be focused on patients with existing pulmonary risk factors, while all patients should be monitored for clinical symptoms of lung issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung toxicity of lomustine in the treatment of progressive gliomas. Seliger, C., Nürnberg, C., Wick, W., et al.[2022]

In a study of 31 patients with relapsed high-grade gliomas, combining radiation therapy with the chemotherapy drug lomustine (CCNU) resulted in a median overall survival of 13.7 months, indicating a potential benefit for patients after relapse.

The treatment was associated with moderate acute toxicity, with some patients experiencing mild to moderate side effects like leucopenia and nausea, but overall patient compliance was good, suggesting the regimen is manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reirradiation and lomustine in patients with relapsed high-grade gliomas. Arcicasa, M., Roncadin, M., Bidoli, E., et al.[2022]

In a study of 28 patients treated for malignant brain tumors, 50% exhibited signs of restrictive lung disease (RLD), with a significant association found between spinal irradiation and the development of RLD.

Patients who received spinal irradiation were 4.3 times more likely to develop RLD compared to those who did not receive this treatment, highlighting spinal irradiation as a potential risk factor for lung complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation. Jakacki, RI., Schramm, CM., Donahue, BR., et al.[2017]

In a study of 16 patients with recurrent high-grade gliomas treated with CCNU (Lomustine), the median progression-free survival was 192 days and overall survival was 282 days, indicating modest efficacy of this salvage treatment.

However, 33.3% of patients experienced severe myelosuppression (grade 3-4), highlighting a significant safety concern that needs to be addressed in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case series of salvage CCNU in high-grade glioma who have previously received temozolomide from a tertiary care institute in Mumbai. Patil, VM., Abhinav, R., Tonse, R., et al.[2018]

A meta-analysis of four randomized controlled trials found that adjuvant lomustine does not significantly improve overall treatment outcomes, such as objective response, complete response, or overall survival, for patients with recurrent glioblastoma.

However, lomustine was associated with a statistically significant increase in 6-month progression-free survival, and it did not lead to a higher incidence of severe adverse events compared to control treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Adjuvant Lomustine to Chemotherapy for Recurrent Glioblastoma: A Meta-analysis of Randomized Controlled Studies. Fu, X., Shi, D., Feng, Y.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nitrosourea therapy for glioblastoma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

ACNU-cisplatin continuous infusion chemotherapy as salvage therapy for recurrent glioblastomas: phase II study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Preradiation chemotherapy with ACNU-CDDP in patients with newly diagnosed glioblastoma: a retrospective analysis. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Lung toxicity of lomustine in the treatment of progressive gliomas. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Reirradiation and lomustine in patients with relapsed high-grade gliomas. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation. [2017]

9. England pubmed.ncbi.nlm.nih.gov

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma. [2021]

10. India pubmed.ncbi.nlm.nih.gov

A case series of salvage CCNU in high-grade glioma who have previously received temozolomide from a tertiary care institute in Mumbai. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Brain tumor chemotherapy using a rat glioma model. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Adjuvant Lomustine to Chemotherapy for Recurrent Glioblastoma: A Meta-analysis of Randomized Controlled Studies. [2022]