SVZ Radiation + Temozolomide for Glioblastoma
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: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Must be taking: Temozolomide
Must not be taking: Avastin
Disqualifiers: Pregnancy, Uncontrolled illness, Prior malignancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests if giving extra radiation to a specific brain area along with standard cancer treatment can help control glioblastoma for a longer time in newly diagnosed patients. The treatment for newly diagnosed glioblastoma changed when radiation therapy plus temozolomide chemotherapy replaced radiation therapy alone.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, you cannot use Avastin or another VEG-F inhibitor before the disease progresses.
What data supports the effectiveness of the drug Temozolomide for treating glioblastoma?
Temozolomide, when used with radiotherapy, has been shown in studies to improve survival in patients with glioblastoma, a type of brain cancer. It is effective in treating various brain tumors and has been used in combination with other therapies to enhance its effectiveness.
12345Is the combination of SVZ Radiation and Temozolomide safe for humans?
Temozolomide, used with radiation for glioblastoma, is generally safe but can cause serious blood-related side effects in some people, like bone marrow failure and severe myelotoxicity (damage to the bone marrow). Rarely, it can also lead to liver damage and aplastic anemia (a condition where the body stops producing enough new blood cells).
26789How is the SVZ Radiation + Temozolomide treatment for glioblastoma different from other treatments?
This treatment is unique because it combines radiation specifically targeting the subventricular zone (SVZ) with Temozolomide, a drug that makes cancer cells more sensitive to radiation. This approach aims to improve the effectiveness of the treatment by focusing on a specific brain area that may influence tumor growth.
210111213Eligibility Criteria
This trial is for adults with newly diagnosed Glioblastoma Multiforme (GBM) who've had surgery but no brain radiation before. They must start treatment within 12 weeks of surgery, have a performance status allowing daily activities with effort or better, and agree to use contraception. Pregnant women, those unwilling to prevent pregnancy, and patients with other serious illnesses or prior cancers (except certain skin cancers and treated cervical cancer) are excluded.Inclusion Criteria
I am 18 years or older and have been diagnosed with GBM.
I had surgery for my brain tumor and will start radiation within 12 weeks post-surgery.
I can care for myself and am up more than 50% of my waking hours.
+7 more
Exclusion Criteria
I have not used Avastin or any VEG-F inhibitor before my cancer progressed.
I am not pregnant or breastfeeding and will use birth control during and up to 12 weeks after the study.
I do not have any severe illnesses that could interfere with the study.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 6 weeks of radiation therapy plus temozolomide chemotherapy. Radiation treatment is modified to deliver a higher dose to the subventricular zone.
6 weeks
5 visits per week (in-person)
Adjuvant Chemotherapy
Participants receive 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle).
6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment. MRIs and clinical evaluations are performed at regular intervals.
24 months
Regular visits at 1, 2, 4, 6, 8, 10, 12, and 24 months post-treatment
Participant Groups
The study tests if targeting the subventricular zone (SVZ)—a brain area containing stem cells—with higher-dose radiation alongside standard chemotherapy (Temozolomide), can control GBM longer than standard therapy alone. Patients will receive this modified radiation plan over six weeks to see if it improves outcomes.
2Treatment groups
Experimental Treatment
Active Control
Group I: Temozolomide plus radiation therapy to the tumor and SVZExperimental Treatment2 Interventions
Patients will be scheduled to receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle).
Patients will receive 60 Gy of radiation therapy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows:
Initial treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series and FLAIR series, plus the bilateral subventricular zone Will be prescribed to 46 Gy in 2 Gy fractions
Cone down treatment plan will include the tumor bed, areas of contrast enhancement on T1 post gadolinium series MRI plus the ipsilateral subventricular zone Will be prescribed to 14 Gy in 2 Gy fractions
Group II: Temozolomide and neural progenitor cell sparing radiationActive Control2 Interventions
Patients will receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle).
Patients will receive 60 Gy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows:
Initial treatment plan will include the tumor bed and MRI abnormalities based on T1 post gadolinium series and FLAIR series.
Will be prescribed to 46 Gy in 2 Gy fractions
Cone down treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series.
Will be prescribed to 14 Gy in 2 Gy fractions
Subventricular Zone radiation is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Temodar for:
- Glioblastoma multiforme
- Anaplastic astrocytoma
🇪🇺 Approved in European Union as Temodal for:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Malignant glioma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The SKCCC at Johns HopkinsBaltimore, MD
Suburban HospitalBethesda, MD
Sibley Memorial HospitalWashington, United States
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Who Is Running the Clinical Trial?
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
Reading Health System FoundationCollaborator
References
Future directions for temozolomide therapy. [2019]Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors. Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents. Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.
Temozolomide-induced liver damage. A case report. [2021]Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists.
[Temozolomide: Temodal]. [2018]The oral alkylating agent, temozolomide (Temodal: TMZ), is the only anticancer drug that has been shown in a phase III study to improve survival in glioblastoma (GBM) when administered with concomitant radiotherapy. Pharmacokinetic studies have documented relatively high concentrations of TMZ in brain tumors and cerebrospinal fluid (20-40% of the area under the plasma concentration curve), and other studies have demonstrated that TMZ is effective for treatment of various brain tumors, including recurrent and newly diagnosed glioma, primary CNS lymphoma, metastatic melanoma, and neuroblastoma. Molecular markers that predict a favorable response to TMZ plus concomitant radiotherapy include methylguanine methyltransferase (MGMT) promoter methylation patients with GBM and chromosome 1p/19q deletion in patients with anaplastic oligodendroglioma or low-grade glioma. Myelosuppression, nausea and constipation are relatively frequent in patients undergoing treatment with TMZ, and prophylaxis against Pneumocystis carinii pneumonia should be instituted. This article will summarize and discuss these issues as well as review ongoing and anticipated studies of TMZ in combination with other anti-cancer therapies.
Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. [2018]Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM.
Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases. [2022]Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5-day oral schedule every 4 weeks.
Persistent bone marrow depression following short-term treatment with temozolomide. [2019]Temozolomide (TMZ) is, in combination with radiotherapy (RT), the treatment of choice for glioblastoma multiforme. Although generally well tolerated, haematological side effects are observed in approximately 1-10% of patients receiving TMZ. We report a case of a patient who developed severe bone marrow failure (BMF) after only 3 weeks of concomitant TMZ. The BMF was grave with no signs of improvement for 12 months, resulting in more than 100 transfusions of blood cells.
Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma. [2018]Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers.
Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]Temozolomide (TMZ) administered daily with radiation therapy (RT) for 6 weeks, followed by adjuvant TMZ for 6 cycles, is the standard therapy for newly diagnosed glioblastoma (GBM) patients. Although TMZ is considered to be a safe drug, it has been demonstrated to cause severe myelotoxicity; in particular, some case reports and small series studies have reported severe myelotoxicity developing during TMZ and concomitant RT. We performed a prospective study to analyze the incidence of early severe myelotoxicity and its possible clinical and genetic factors.
Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]Temozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported.
Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. [2022]Concurrent temozolomide (TMZ) and radiotherapy is the new standard of care for patients with newly diagnosed glioblastoma. In 51 consecutive patients treated according to this regimen, 7 patients (14%) manifested surgically confirmed early necrosis without evidence of recurrent tumor. This observation suggests that daily TMZ may represent a potent radiosensitizing regimen.
Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial. [2022]To test the hypothesis on prolonged survival in glioblastoma cases with increased subventricular zone (SVZ) radiation dose. Sixty glioblastoma cases were previously treated with adjuvant radiotherapy and Temozolamide. Ipsilateral, contralateral and bilateral SVZs were contoured and their doses were retrospectively evaluated. Median follow-up, progression free survival (PFS) and overall survival (OS) were 24.5, 8.5 and 19.3 months respectively. Log-rank tests showed a statistically significant correlation between contralateral SVZ (cSVZ) dose > 59.2 Gy (75th percentile) and poor median PFS (10.37 [95% CI 8.37-13.53] vs 7.1 [95% CI 3.5-8.97] months, p = 0.009). cSVZ dose > 59.2 Gy was associated with poor OS in the subgroup with subtotal resection/biopsy (HR: 4.83 [95% CI 1.71-13.97], p = 0.004). High ipsilateral SVZ dose of > 62.25 Gy (75th percentile) was associated with poor PFS in both subgroups of high performance status (HR: 2.58 [95% CI 1.03-6.05], p = 0.044) and SVZ without tumoral contact (HR: 10.57 [95% CI 2.04-49], p = 0.008). The effect of high cSVZ dose on PFS lost its statistical significance in multivariate Cox regression analysis. We report contradictory results compared to previous publications. Changing the clinical practice based on retrospective studies which even do not indicate consistent results among each other will be dangerous. We need carefully designed prospective randomized studies to evaluate any impact of radiation to SVZ in glioblastoma.
Impact of the per-operatory application of GLIADEL wafers (BCNU, carmustine) in combination with temozolomide and radiotherapy in patients with glioblastoma multiforme: efficacy and toxicity. [2018]For the last few years wafers of Gliadel have been inserted into the operation cavity in patients with glioblastoma multiforme. This is followed by concurrent radio-chemotherapy with temozolomide (TMZ) according to the Stupp protocol. Only a few studies have investigated this kind of treatment regimen and the impact in terms of survival and toxicity of the combination of Gliadel with TMZ and radiotherapy.
The inhibition of proliferation and migration of glioma spheroids exposed to temozolomide is less than additive if combined with irradiation. [2018]The aim of this study was to investigate the effect of temozolomide (TZM) in combination with X-rays on proliferation and migration in human glioma spheroids. Multicellular spheroids were derived from GaMg and U87 cell lines. Spheroids were treated with various concentrations of TZM (5 micromol, 0.025 mmol, 0.05 mmol) and irradiation (RT). Proliferation and migration assays were performed. For GaMg spheroids, the proliferation inhibition was 30% (RT), 71%, 79%, 85% (for various TZM concentrations) and 78%, 83%, 90% following RT+TZM. For U87 spheroids, the inhibition of proliferation was 52% (RT), 62%, 78%, 88% (TZM), and 73%, 87%, 92% (RT+TZM). Inhibition of migration for GaMg was 30% (RT), 37%, 63%, 78% (TZM), and 56%, 75%, 84% (RT+TZM). For U87, migration inhibition was 29% (RT), 48%, 52%, 67% (TZM), and 62%, 67%, 73% (RT+TZM). Radiotherapy enhancement ratio (RER) of GaMg/U87 spheroid proliferation was 1.4/1.7 (5 micromol TZM), 1.3/1.8 (0.025 mmol TZM), and 1.4/1.4 (0.05 mmol TZM). RER for migration of GaMg/U87 was 2.2/1.9 (5 micromol TZM), 1.7/1.8 (0.025 mmol TZM), and 1.5/1.4 (0.05 mmol TZM). In terms of inhibition of proliferation and migration, irradiation can lead to an enhancement of the TZM effect in human glioma spheroids, which is less than additive.