Carmustine Wafers for Brain Tumor

Recruiting at 2 trial locations

Overseen By Project Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Michele Aizenberg, MD

Must not be taking: Anticoagulants, Antiplatelets, NSAIDs

Disqualifiers: Lymphoma, Neurodegenerative disorder, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to see if adding GLIADEL to the site where the tumor was removed works as well as just having the tumor removed with radiation treatment done within six weeks after the surgery to keep the cancer from coming back.

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, if you are taking anticoagulants or antiplatelet agents, including NSAIDs, you may need to stop them before surgery.

What data supports the effectiveness of the treatment Carmustine Wafers for brain tumors?

Carmustine wafers have been shown to improve survival and quality of life in patients with malignant glioma, especially when used alongside other treatments like chemotherapy and radiotherapy. Clinical trials and case studies have demonstrated that these wafers can effectively increase survival time compared to traditional treatments alone. ^{1 2 3 4 5}

Is carmustine (BCNU) wafer treatment generally safe for humans?

Carmustine wafers, used for brain tumors like glioblastoma, have been studied for safety and are generally considered safe, though they can cause side effects such as brain swelling, seizures, fluid leakage, and slow wound healing. Most side effects occur shortly after surgery, and doctors take steps to manage them. ^{1 4 6 7 8}

How does the carmustine wafer treatment differ from other brain tumor treatments?

Carmustine wafers are unique because they are implanted directly into the brain during surgery, allowing for localized chemotherapy delivery to the tumor site. This method avoids the high toxicity and short half-life issues associated with traditional systemic chemotherapy, providing immediate treatment to residual tumor cells and potentially improving survival and quality of life for patients with malignant glioma. ^{1 2 3 6 7}

Research Team

Michele Aizenberg, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for adults with certain types of solid cancer that has spread to the brain, who are planning surgery to remove one or two tumors. They should be in good physical condition (Karnofsky Score ≥ 70), not have had prior treatment on the area, and expect to live at least 3 more months. Pregnant women and those unable or unwilling to follow study rules can't join.

Inclusion Criteria

Your blood's ability to clot is within a certain range.

I am at least 18 years old, or 19 if I live in Nebraska.

The subject is willing and able to consent to and abide by the protocol

Exclusion Criteria

You cannot have an MRI scan.

I cannot stop my blood thinners or NSAIDs for surgery.

You are already taking part in another medical research study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Participants undergo surgical resection of the tumor. Randomization occurs at the time of surgery to either GLIADEL placement or SRS post-operatively.

Immediate

1 visit (in-person)

Post-operative Treatment

Participants receive either GLIADEL wafers applied to the resection cavity or SRS to the resection cavity within 6 weeks post-surgery. Any other tumors will receive SRS.

6 weeks

Follow-up

Participants are monitored for local recurrence and neurocognitive changes. The genome of the metastatic brain tumor is compared to their primary and germline for identification of alterations.

12 months

Treatment Details

Interventions

• Carmustine

Trial Overview The study compares adding GLIADEL wafers directly into the site after tumor removal versus just having radiation therapy post-surgery. The goal is to see which method better prevents cancer from returning.

Participant Groups

Group I: GLIADEL Arm Experimental Treatment 1 Intervention

Once the tumor has been removed, GLIADEL wafers will be applied to the resection cavity. The number of wafers used will be determined by the size of the cavity. Enough wafers should be used so that as much of the cavity is covered as possible.

Group II: Standard of Care Arm Active Control 1 Intervention

The tumor will be removed surgically. Within 6 weeks after surgery, the resection will be treated with stereotactic radiosurgery (SRS).

Who Is Running the Clinical Trial?

Michele Aizenberg, MD

Lead Sponsor

Trials

1

Recruited

100+

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Arbor Pharmaceuticals, Inc.

Industry Sponsor

Trials

17

Recruited

2,500+

Findings from Research

A review of 29 studies involving BCNU wafers for treating malignant gliomas found that adverse event rates were generally low and comparable to those in initial registration studies, with common issues including seizures (19-33%) and healing abnormalities (14-16%).

The safety profile of BCNU wafers remains consistent across different treatment regimens, suggesting that with proper management, the risk of complications can be minimized, making it a viable option for patients with recurrent glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience. Sabel, M., Giese, A.[2019]

Carmustine (BCNU) wafers are a local treatment for malignant glioma that improve patient survival and quality of life after tumor resection, avoiding the high toxicity of systemic chemotherapy.

In a case series of four patients, including those with recurrent glioblastoma, BCNU wafers were well tolerated and resulted in survival times ranging from 56 to 132 weeks, which is significantly better than the average survival of 58 weeks with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating BCNU wafers into malignant glioma treatment: European case studies. Balossier, A., Dörner, L., Emery, E., et al.[2021]

Biodegradable wafers containing carmustine (BCNU) have been approved by the FDA for treating newly diagnosed high-grade glioma and recurrent glioblastoma, highlighting their efficacy as a localized chemotherapy option.

The ongoing VIGILANT registry, which includes up to 500 patients and will follow them for 3 years, aims to assess the real-world effectiveness of BCNU wafers while considering various tumor types and molecular markers, with interim results expected before the final analysis in 2024.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the 500-patient, 3-year, and prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry. Lillehei, KO., Kalkanis, SN., Liau, LM., et al.[2019]

Carmustine (BCNU) wafer implantation has been positively received by Japanese neurosurgeons since its introduction in 2013, as it is believed to improve the prognosis for patients with high-grade glioma (HGG).

Neurosurgeons are actively managing adverse effects associated with the treatment, such as cerebral edema and postoperative complications, indicating a proactive approach to patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative BCNU Wafer Implantation for High-Grade Glioma--A Questionnaire Targeting Japanese Neurosurgeons]. Ishikawa, E., Yamamoto, T.[2016]

In a study of 15 patients with glioblastoma (GBM) using BCNU wafers, BCNU concentration peaked one hour after surgery and remained relatively high for seven days, but did not significantly correlate with tumor progression or overall survival.

Patients with less-invasive GBM types showed a potential survival benefit from higher BCNU concentrations, while those with highly invasive GBM had early recurrences, suggesting that the effectiveness of BCNU may vary based on tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Interstitial Chemotherapy with Carmustine (BCNU) Wafers Effective against Local Recurrence of Glioblastoma? A Pharmacokinetic Study by Measurement of BCNU in the Tumor Resection Cavity. Ohnishi, T., Yamashita, D., Inoue, A., et al.[2022]

In a study of 36 patients treated with BCNU wafers for malignant glioma, 58% developed a surgical bed cyst within one month, with 48% of those being symptomatic, indicating a common post-treatment occurrence.

Despite the high incidence of bed cysts, they generally behaved benignly, resolving with corticosteroid treatment and not leading to permanent neurological deficits, suggesting that while monitoring is necessary, the overall safety profile remains reassuring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first 3 months after BCNU wafers implantation in high-grade glioma patients: clinical and radiological considerations on a clinical series. Della Puppa, A., Rossetto, M., Ciccarino, P., et al.[2016]

Polymeric drug-delivery systems, like BCNU wafers, can effectively deliver chemotherapy directly to glioblastoma tumor sites, potentially improving local drug concentrations while minimizing systemic side effects.

Studies have shown that BCNU wafers, when used as monochemotherapy alongside radiation therapy, can significantly increase median overall survival in patients with newly diagnosed high-grade gliomas, although further phase III studies are needed to confirm their efficacy when combined with the standard Stupp regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polymeric drug delivery for the treatment of glioblastoma. Wait, SD., Prabhu, RS., Burri, SH., et al.[2018]

In a study of 40 patients with inoperable glioblastoma multiforme, the combination of carmustine (BCNU) and temozolomide showed a promising objective response rate of 42.5%, indicating its potential effectiveness as a first-line chemotherapy before and after radiotherapy.

The treatment was generally well-tolerated, with manageable grade 3-4 toxicities such as thrombocytopenia and neutropenia, and no patients discontinued treatment due to side effects, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme. Barrié, M., Couprie, C., Dufour, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Incorporating BCNU wafers into malignant glioma treatment: European case studies. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Rationale and design of the 500-patient, 3-year, and prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[Intraoperative BCNU Wafer Implantation for High-Grade Glioma--A Questionnaire Targeting Japanese Neurosurgeons]. [2016]

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

Is Interstitial Chemotherapy with Carmustine (BCNU) Wafers Effective against Local Recurrence of Glioblastoma? A Pharmacokinetic Study by Measurement of BCNU in the Tumor Resection Cavity. [2022]

6. Austria pubmed.ncbi.nlm.nih.gov

The first 3 months after BCNU wafers implantation in high-grade glioma patients: clinical and radiological considerations on a clinical series. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Polymeric drug delivery for the treatment of glioblastoma. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme. [2022]