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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment TTFields + SRS + Temozolomide for Glioblastoma?

Research shows that combining stereotactic radiosurgery (SRS) with temozolomide (a chemotherapy drug) can be effective for treating glioblastoma, as SRS can target tumors precisely and temozolomide can enhance the effect of radiation on tumor cells. Studies have found that this combination can help control tumor growth and is generally well-tolerated by patients. ^{1 2 3 4 5}

Is the combination of TTFields, SRS, and Temozolomide safe for humans?

Research shows that combining stereotactic radiosurgery (SRS) with temozolomide (TMZ) has been studied for safety in treating brain conditions like glioblastoma and brain metastases. These studies generally focus on the safety of using SRS and TMZ together, indicating that this combination has been evaluated for its safety profile in humans. ^{1 2 3 6 7}

How is the treatment TTFields + SRS + Temozolomide for glioblastoma different from other treatments?

This treatment combines tumor treating fields (TTFields), a non-invasive therapy that disrupts cancer cell division, with stereotactic radiosurgery (SRS) and the chemotherapy drug temozolomide. The combination is unique because TTFields and radiotherapy have synergistic effects, potentially enhancing the treatment's effectiveness compared to using temozolomide alone. ^{1 8 9 10 11}

What is the purpose of this trial?

The purpose of this study is to determine the safety and efficacy of the combination therapy of TTFields + SRS+ Temozolomide (TMZ) for newly diagnosed glioblastoma (GBM).

Research Team

Scott G Soltys

Principal Investigator

Stanford Universiy

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas. [2022]

2. England 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. [2021]

3. Cyprus 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Chemosensitized radiosurgery for recurrent brain metastases. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases. [2020]

6. France pubmed.ncbi.nlm.nih.gov

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Initial experience with scalp sparing radiation with concurrent temozolomide and tumor treatment fields (SPARE) for patients with newly diagnosed glioblastoma. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treating Glioblastoma With Tumor-Treating Fields Therapy. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. [2023]