TTFields + SRS + Temozolomide for Glioblastoma

Overseen By Aniket Pratapneni

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must be taking: Temozolomide

Must not be taking: Tuberculosis drugs, HIV drugs

Disqualifiers: Cirrhosis, Prior malignancy, Severe illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals newly diagnosed with glioblastoma, an aggressive brain cancer. The treatment combines a wearable device called Optune, stereotactic radiosurgery (a precise form of radiation therapy), and the chemotherapy drug temozolomide. Researchers aim to determine the safety and effectiveness of this combination. Individuals recently diagnosed with glioblastoma who have not previously undergone chemotherapy or radiation may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications for tuberculosis or HIV, as they interact with temozolomide. You also cannot take other chemotherapy, investigational agents, or biologic agents for cancer treatment during the trial.

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

Research has shown that temozolomide (TMZ) is generally well-tolerated by patients. In a study involving 347 patients with brain tumors, researchers carefully assessed the safety of TMZ. Most patients managed the treatment well, though some experienced serious side effects, such as low blood cell counts, which occasionally required stopping the treatment.

Optune and stereotactic radiosurgery (SRS) both treat brain conditions. Optune, a device worn on the head, has been used safely in other treatments. SRS, a precise form of radiation therapy, is usually well-tolerated.

This trial is in an early phase, aiming to assess the safety of these treatments when used together. While each treatment has been used before, their combination is new. Safety data from this phase will provide insight into how well patients can tolerate all three treatments working together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for glioblastoma because it brings together three innovative approaches. Unlike traditional treatments that often rely solely on chemotherapy or radiation, this approach includes Optune, a device that uses Tumor Treating Fields (TTFields) to disrupt cancer cell division. Additionally, the use of Stereotactic Radiosurgery (SRS) allows for precise targeting of the tumor with radiation, minimizing damage to surrounding healthy tissue. Temozolomide, an oral chemotherapy drug, rounds out the treatment, offering a comprehensive attack on the cancer. This multi-pronged strategy holds the potential to enhance effectiveness and improve outcomes for patients battling this aggressive brain cancer.

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

Research shows that Temozolomide (TMZ) can significantly improve outcomes for patients with glioblastoma, a type of brain cancer. Studies have found that combining Temozolomide with radiation therapy increases survival rates compared to radiation alone. For example, one study found that 70% of patients survived for 10 years with the combination, while only 47% survived with just radiation. Additionally, using Temozolomide for a longer period may enhance survival without increasing side effects. These findings suggest that Temozolomide effectively improves glioblastoma treatment. In this trial, participants will receive a combination of Temozolomide, Stereotactic Radiosurgery (SRS), and the Optune device (TTFields) to evaluate the effectiveness of this combined approach. ^{1 6 7 8 9}

Who Is on the Research Team?

Scott G Soltys

Principal Investigator

Stanford Universiy

Are You a Good Fit for This Trial?

Adults diagnosed with newly confirmed glioblastoma, able to undergo MRI, and have good organ function. Participants must not be pregnant or nursing, should not have other severe illnesses or skin conditions that could interfere with treatment, and cannot be on certain medications like those for tuberculosis or HIV.

Inclusion Criteria

My platelet count is healthy without needing blood transfusions in the past week.

I am a woman who can have children and have a negative pregnancy test, or I am postmenopausal or surgically sterile.

Bilirubin ≤ 1.5 × upper limit of normal (ULN), except for subjects with documented history of Gilbert's disease

Exclusion Criteria

I am not on medication for tuberculosis or HIV.

Pregnant or nursing females will be excluded from the study

History of inability to tolerate MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tumor Treating Fields with 5-day hypofractionated stereotactic radiosurgery and concurrent temozolomide

8 days

Daily visits for radiation and monitoring

Adjuvant Chemotherapy

Participants receive standard of care adjuvant chemotherapy and routine surveillance brain MRI scans

5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Optune
• Stereotactic Radiosurgery (SRS)
• Temozolomide

Trial Overview The trial is testing a combination therapy for brain cancer (glioblastoma) using Tumor Treating Fields (TTFields), Stereotactic radiosurgery (SRS), and the chemotherapy drug Temozolomide to evaluate safety and effectiveness.

How Is the Trial Designed?

Group I: Novo-TTF Experimental Treatment 4 Interventions

Day 1: Subjects will wear the Optune (TTFields device) for ≥ 18 hours/day. They will take off the device when receiving stereotactic radiosurgery and brain MRI scans. Days 1 to 8: Subjects will take oral temozolomide 75 mg/m2/day Days 2 to 8: Subjects will receive stereotactic radiosurgery (total of 35 Gy) divided equally over 5 days • After the interventional treatment, subjects will receive standard of care adjuvant chemotherapy and routine surveillance brain MRI scans.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Published Research Related to This Trial

The maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) combined with temozolomide for newly diagnosed glioblastoma was determined to be 40 Gy, with limited dose-limiting toxicities observed in a study of 30 patients.

While some patients experienced late grades 1-2 adverse radiation effects (ARE), these did not significantly impact overall survival, suggesting that the treatment is relatively safe and effective, with median overall survival reaching 14.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes. Azoulay, M., Chang, SD., Gibbs, IC., et al.[2021]

Combining CyberKnife stereotactic radiosurgery (SRS) with a dose-dense regimen of temozolomide (TMZ) significantly improved median survival (12 months vs. 7 months) and 6-month progression-free survival (66.7% vs. 18%) in patients with recurrent glioblastoma multiforme (GBM).

While the combination treatment showed better outcomes, over 40% of patients experienced grade 3 hematological toxicity, indicating a need for careful monitoring of side effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas. Conti, A., Pontoriero, A., Arpa, D., et al.[2022]

In a phase II trial involving 54 patients with complex brain metastases, the combination of hypofractionated stereotactic radiotherapy (HFSRT) and temozolomide (TMZ) was found to be well tolerated, with only a small percentage experiencing severe side effects.

The treatment resulted in a median overall survival of 17.4 months and high local control rates of 96% at 1 year and 82% at 2 years, suggesting it could significantly improve outcomes for patients with challenging brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases. Bi, N., Ma, Y., Xiao, J., et al.[2020]

In a study of 128 patients with brain metastases from non-small cell lung cancer, synchronous stereotactic radiotherapy (SRT) combined with temozolomide (TMZ) and whole brain radiotherapy (WBRT) significantly improved overall survival (OS) and progression-free survival (PFS) compared to SRT with WBRT alone, with median OS of 13.1 months and PFS of 11.2 months in the TMZ group.

While the combination treatment led to a higher incidence of nausea and vomiting (67.2% vs. 43.8%), other adverse reactions were similar between the two groups, indicating that the treatment is generally tolerable despite some side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of synchronous stereotactic radiotherapy with temozolomide combined with whole brain radiotherapy in treating brain metastases originating from non-small cell lung cancer. Liu, P., Ren, R., You, D., et al.[2021]

Salvage stereotactic radiotherapy (SRT) using CyberKnife for recurrent gliomas showed an acceptable safety profile, with only 11.4% of patients experiencing significant toxicity, specifically radiation-induced brain necrosis.

The treatment resulted in a median overall survival of 9 months and a progression-free survival of 3 months, indicating that SRT can be a viable option for patients with recurrent gliomas after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. Adachi, K., Hayashi, K., Kagawa, N., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11275351/

Temozolomide (TMZ) in the Treatment of Glioblastoma ... Prolonged TMZ therapy (>6 cycles) may result in improved survival of patients with GBM without increasing the frequency of hematologic side ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-13757-1

The role of temozolomide as adjuvant therapy in glioblastoma ... TMZ has been shown to significantly improve patient outcomes, notably increasing the median overall survival compared to RT alone [2]. This ...

3. ecog-acrin.org ecog-acrin.org/press-release-adding-the-chemotherapy-pill-temozolomide-to-radiation-therapy-improves-survival-in-adult-patients-with-glioma-a-slow-growing-type-of-brain-cancer/

Clinical trial finds that adding the chemotherapy pill ... “We found that the 10-year survival rate was 70% with the combined treatment with temozolomide chemotherapy and radiation, compared to 47% with ...

4. spandidos-publications.com spandidos-publications.com/10.3892/ol.2024.14551

Temozolomide based treatment in glioblastoma: 6 vs. 12 ... The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.

5. academic.oup.com academic.oup.com/noa/article/7/1/vdaf084/8120832

Second-line temozolomide in first recurrent MGMT-methylated ... Among patients receiving temozolomide only, stable disease or partial response was achieved in 53.3%, with a progression-free survival rate at 6 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/021029s031lbl.pdf

TEMODAR (temozolomide) Label - accessdata.fda.gov In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 9.5% (6/63) of patients over age 70 experienced Grade 4 neutropenia or ...

7. karger.com karger.com/ocl/article/103/9/815/919076/Post-Marketing-Safety-of-Temozolomide-A

Post-Marketing Safety of Temozolomide: A ... In general, TMZ is well tolerated by patients. However, a small number may experience severe side effects, which can lead to discontinuation of ...

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1437436/full

Comprehensive understanding of the adverse effects ... In a clinical trial involving 347 patients with malignant glioma treated with TMZ, the safety of TMZ was clearly evaluated, and the most common ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/temozolomide-oral-route/description/drg-20066228

Temozolomide (oral route) - Side effects & dosage Temozolomide is used to treat specific types of brain cancer (eg, glioblastoma ... Safety and efficacy have not been established. .