Berubicin for Glioblastoma

Not currently recruiting at 68 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, berubicin and lomustine, for glioblastoma, a challenging brain cancer. The goal is to determine which treatment extends and improves life after standard first-line treatments fail. Participants will be divided into two groups: one will receive berubicin, and the other will receive lomustine, a chemotherapy drug, to compare their effects on survival and tumor progression. Ideal participants have glioblastoma that has returned or progressed after initial treatment and have not received more than one prior line of therapy. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that berubicin is generally well-tolerated by patients with glioblastoma multiforme, especially when other treatments have failed. Most patients can undergo this treatment without major issues. Ongoing studies closely monitor berubicin to ensure its safety.

In contrast, lomustine, already approved by the FDA for certain cancers, has a well-established safety profile from years of use in medical practice.

Both treatments are under study to confirm their safety for patients. However, researchers continue to test berubicin, aiming to compare patient tolerance to that of lomustine. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, which often include surgical resection, radiation, and chemotherapy with temozolomide, Berubicin is unique because it is an anthracycline that can cross the blood-brain barrier to target brain tumors directly. Most treatments for glioblastoma struggle with this barrier, making Berubicin's ability to penetrate it a significant advantage. Researchers are excited about Berubicin's potential to target the tumor more effectively while minimizing damage to healthy brain tissue. Additionally, its administration as an intravenous infusion over a short cycle offers a different regimen compared to traditional oral chemotherapies, which might enhance patient compliance and quality of life.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research suggests that Berubicin, one of the treatments studied in this trial, could be promising for treating glioblastoma, an aggressive brain cancer. Berubicin can cross the blood-brain barrier, which many drugs cannot do. In earlier studies, Berubicin showed lasting effects, with some patients experiencing significant benefits like stable disease or long-term survival. One patient even lived more than 13 years after treatment. In another study, Berubicin helped animals with brain tumors live longer compared to the standard treatment, temozolomide. While these results are encouraging, more research is needed to confirm Berubicin's effectiveness. Participants in this trial may receive Berubicin or the active comparator, Lomustine, to evaluate their effectiveness in treating glioblastoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Sandra Silberman, MD, PhD

Principal Investigator

CNS Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

Citations

1. cnspharma.com cnspharma.com/ir/press-releases/cns-pharmaceuticals-announces-primary-analysis-of-berubicin-in-second-line-treatment-of-glioblastoma-multiforme-44471506

CNS Pharmaceuticals Announces Primary Analysis of ... Berubicin showed clinically relevant outcomes comparable to Lomustine across multiple endpoints, but not a statistically significant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04762069

NCT04762069 | A Study of Berubicin in Adult Subjects With ... A Phase 1 clinical trial of berubicin in patients with primary CNS malignancies demonstrated a durable response (one subject alive 13+ years) as well as stable ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10639365/

CTNI-35. A RANDOMIZED, CONTROLLED TRIAL OF ... RESULTS: of a Phase 1 dose-escalation study with 25 patients evaluable for efficacy showed 1 complete response (14+ years), 1 partial response durable for 12 ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii112/7890301

A RANDOMIZED, CONTROLLED TRIAL OF BERUBICIN VS ... Berubicin, derived from doxorubicin (Dox), appears to cross the BBB and has shown significant central nervous system (CNS) uptake and anti-tumor ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS2083

Design and initiation of an adaptive, randomized ... In models of intracranial orthotopic gliomas, Berubicin prolonged survival when compared to temozolomide, currently a standard of care in GBM.

6. biospace.com biospace.com/cns-pharmaceuticals-nasdaq-cnsp-presents-updated-safety-data-from-ongoing-potentially-pivotal-study-evaluating-berubicin-in-advance-of-the-pre-planned-interim-analysis-of-efficacy

CNS Pharmaceuticals (NASDAQ: CNSP) Presents ... CNS Pharmaceuticals, Inc. today announced the presentation of updated safety data from the ongoing potentially pivotal study evaluating Berubicin.

7. onclive.com onclive.com/view/berubicin-demonstrates-early-promise-in-recurrent-or-refractory-glioblastoma-multiforme

Berubicin Demonstrates Early Promise in Recurrent or ... Berubicin was found to have acceptable tolerability when administered as second-line treatment in patients with recurrent or refractory glioblastoma multiforme.