Carmustine Wafers for Brain Tumor
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Michele Aizenberg, MD
Must not be taking: Anticoagulants, Antiplatelets, NSAIDs
Disqualifiers: Lymphoma, Neurodegenerative disorder, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
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.12345
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.15678
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.13467
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
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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.
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Trial 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 (Alkylating agents)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: GLIADEL ArmExperimental Treatment1 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 ArmActive Control1 Intervention
The tumor will be removed surgically. Within 6 weeks after surgery, the resection will be treated with stereotactic radiosurgery (SRS).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Henry FordDetroit, MI
Ohio State UniversityColumbus, OH
University of Nebraska Medical CenterOmaha, NE
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Who Is Running the Clinical Trial?
Michele Aizenberg, MDLead Sponsor
University of NebraskaLead Sponsor
Arbor Pharmaceuticals, Inc.Industry Sponsor
References
Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience. [2019]Carmustine (1,3-bis [2-chloroethyl]-1-nitrosourea, or BCNU) wafers are approved for recurrent glioblastoma and newly diagnosed malignant glioma (MG). Based on considerable clinical experience and use in multimodal regimens, the safety of BCNU wafers needs a re-evaluation.
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]The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel®) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC)all was calculated from BCNU concentration curves, and the relationships between AUCall and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUCall tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUCall were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM.
Incorporating BCNU wafers into malignant glioma treatment: European case studies. [2021]Carmustine (BCNU: N,N'-bis[2-chloroethyl]-N-nitrosourea) wafers are a local chemotherapeutic agent for the treatment of malignant glioma. They avoid the problems of high toxicity and short half-life associated with systemic delivery, and can bridge the traditional 'treatment gap' between surgery and subsequent conventional chemo- or radiotherapy. Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation. In practice, clinicians may use BCNU wafers in conjunction with other radio- and chemotherapies, in order to maximize the chance of a beneficial patient outcome. The purpose of these case reports is to exemplify how four experienced European clinicians employ BCNU wafers for the management of malignant glioma, and to illustrate how BCNU wafers can be effectively incorporated into treatment regimens. Four patients are described in whom BCNU wafers were implanted during the course of treatment for glioblastoma multiforme, the most severe and common type of malignant glioma. These include three patients with recurrent disease, and a single patient with a newly diagnosed tumour. All four patients received additional radio- and chemotherapy as appropriate. Treatment was well tolerated and patient survival from diagnosis ranged from 56 to 132 weeks. This compared favourably with the survival of approximately 58 weeks seen in the recent EORTC-NCIC clinical trial of combined radiotherapy with concomitant and adjuvant temozolomide. BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours.
Rationale and design of the 500-patient, 3-year, and prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT registry. [2019]Implantation of biodegradable wafers impregnated with carmustine (BCNU) is one of the few chemotherapeutic modalities that have been evaluated in Phase III trials and approved by the US FDA for treatment of newly diagnosed high-grade glioma and recurrent glioblastoma. Enrolling up to 500 patients for 3-year follow-up at over 30 sites, the prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) will evaluate BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular tumor analysis. Subgroup analyses will include tumor type, molecular marker status, and treatment combinations. Interim analyses from the VIGILANT registry will be reported until complete results are available in 2024.
[Intraoperative BCNU Wafer Implantation for High-Grade Glioma--A Questionnaire Targeting Japanese Neurosurgeons]. [2016]Carmustine (BCNU) wafer implantation has been used in Japanese patients after resection of high-grade glioma (HGG) since 2013. Wafer implantation plays an important role in improving the prognosis of HGG patients, but it often causes particular changes as observed on neuroimaging and various adverse effects (AEs). Here, we conducted a questionnaire-based survey of Japanese neurosurgeons to determine how they feel about this treatment based on their actual observations. Most neurosurgeons had a positive impression of the treatment based on previous evidence of clinical effectiveness. Additionally, we found that the Japanese neurosurgeons are taking measures to cope with some AEs including cerebral edema, postoperative convulsions, cerebrospinal fluid leakage, and protracted wound healing.
The first 3 months after BCNU wafers implantation in high-grade glioma patients: clinical and radiological considerations on a clinical series. [2016]Carmustine (1,3-bis[2-chloroetyl]-1-nitrosurea (BCNU)) wafers are approved for the local treatment of newly diagnosed and recurrent malignant glioma. Reassuring data on both safety and efficacy of treatment have been previously reported by phase III studies. Although most of related adverse events are reported in the first few months after surgery, there is a lack in the literature of radiological data regarding this period. Few anecdotal experiences have been reported about surgical bed cyst occurrence. The aim of our study is to analyse the radiological course of patients treated with wafers implantation focusing on the relationship between radiological data, and in particular bed cyst occurrence, and safety data.
Polymeric drug delivery for the treatment of glioblastoma. [2018]Glioblastoma (GBM) remains an almost universally fatal diagnosis. The current therapeutic mainstay consists of maximal safe surgical resection followed by radiation therapy (RT) with concomitant temozolomide (TMZ), followed by monthly TMZ (the "Stupp regimen"). Several chemotherapeutic agents have been shown to have modest efficacy in the treatment of high-grade glioma (HGG), but blood-brain barrier impermeability remains a major delivery obstacle. Polymeric drug-delivery systems, developed to allow controlled local release of biologically active substances for a variety of conditions, can achieve high local concentrations of active agents while limiting systemic toxicities. Polymerically delivered carmustine (BCNU) wafers, placed on the surface of the tumor-resection cavity, can potentially provide immediate chemotherapy to residual tumor cells during the standard delay between surgery and chemoradiotherapy. BCNU wafer implantation as monochemotherapy (with RT) in newly diagnosed HGG has been investigated in 2 phase III studies that reported significant increases in median overall survival. A number of studies have investigated the tumoricidal synergies of combination chemotherapy with BCNU wafers in newly diagnosed or recurrent HGG, and a primary research focus has been the integration of BCNU wafers into multimodality therapy with the standard Stupp regimen. Overall, the results of these studies have been encouraging in terms of safety and efficacy. However, the data must be qualified by the nature of the studies conducted. Currently, there are no phase III studies of BCNU wafers with the standard Stupp regimen. We review the rationale, biochemistry, pharmacokinetics, and research history (including toxicity profile) of this modality.
Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme. [2022]The aim of this study was to evaluate the efficacy and safety of carmustine (BCNU) in combination with temozolomide as first-line chemotherapy before and after radiotherapy (RT) in patients with inoperable, newly diagnosed glioblastoma multiforme (GBM).