Optune + Temozolomide + Pembrolizumab for Brain Cancer
(EF-41 Trial)
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: NovoCure GmbH
Must be taking: Temozolomide
Must not be taking: PD-1 inhibitors
Disqualifiers: Immunodeficiency, Pneumonitis, Other malignancy, others
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a multicenter, two-arm, randomized, double-blind, placebo-controlled study of Optune® (Tumor Treating Fields at 200 kHz) together with maintenance Temozolomide (TMZ) chemotherapy agent and pembrolizumab compared to Optune® together with maintenance TMZ and placebo in newly diagnosed Glioblastoma (GBM) patients. The primary objective of the study is to evaluate the Overall Survival (OS).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain cancer therapies or high doses of steroids. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the treatment Optune + Temozolomide + Pembrolizumab for brain cancer?
Research shows that pembrolizumab, one of the drugs in this treatment, has shown activity in treating various cancers, including melanoma and non-small-cell lung cancer, even when these cancers have spread to the brain. This suggests it might help in treating brain cancer as well.
12345Is the combination of Optune, Temozolomide, and Pembrolizumab safe for brain cancer treatment?
Temozolomide is generally safe and well-tolerated, with common side effects like fatigue, nausea, and mild blood-related issues. Severe blood problems are rare. No specific safety data for the combination with Optune and Pembrolizumab is provided.
678910What makes the Optune + Temozolomide + Pembrolizumab treatment unique for brain cancer?
This treatment combines Optune, a device that uses electric fields to disrupt cancer cell division, with Temozolomide, a chemotherapy drug, and Pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells. This combination is unique because it integrates different approaches—electric fields, chemotherapy, and immunotherapy—to target brain cancer from multiple angles.
610111213Eligibility Criteria
This trial is for adults over 18 with a new diagnosis of Glioblastoma who have recovered from surgery and completed standard chemoradiotherapy. Participants must be in good physical condition (ECOG 0-1) and, if taking corticosteroids, on a stable or decreasing dose. They should agree to use the Optune device alongside maintenance Temozolomide chemotherapy.Inclusion Criteria
I have recovered from surgery to remove as much of my tumor as possible.
I have been newly diagnosed with GBM as per WHO 2021 standards.
I've finished standard chemoradiotherapy for my condition.
+5 more
Exclusion Criteria
I haven't had any cancer treatment or experimental drugs in the last 4 weeks.
I have been treated with immunotherapy targeting PD-1, PD-L1, PD-L2, or other T-cell receptors.
My cancer has spread to the lower part of my brain or its lining.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Optune® with maintenance Temozolomide and either pembrolizumab or placebo
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the combination of the Optune device with Temozolomide chemotherapy and Pembrolizumab versus the same setup but replacing Pembrolizumab with a placebo. The main goal is to see which combination helps patients live longer.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Treatment GroupExperimental Treatment3 Interventions
Group II: Control GroupPlacebo Group3 Interventions
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Kentucky Medical CenterLexington, KY
UF Health NeuromedicineGainesville, FL
Swedish Medical CenterSeattle, WA
Hoag Memorial Hospital PresbyterianNewport Beach, CA
More Trial Locations
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Who Is Running the Clinical Trial?
NovoCure GmbHLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC).
Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. [2020]Pembrolizumab is active in melanoma, but activity in patients with untreated brain metastasis is less established. We present long-term follow-up of pembrolizumab-treated patients with new or progressing brain metastases treated on a phase II clinical trial ( ClinicalTrials.gov identifier: NCT02085070).
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study.
Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma.
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.
Temozolomide for treating brain metastases. [2019]The metastasis of solid tumors to the brain is associated with a poor prognosis despite aggressive treatment. Available treatment options are limited, as many chemotherapeutic agents do not penetrate the blood-brain barrier. Temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) is a novel chemotherapeutic agent with a good safety profile that crosses the blood-brain barrier and has shown activity against many human solid tumors. In two phase II trials of temozolomide in heavily pretreated patients with various solid tumor brain metastases, temozolomide was safe and generally well tolerated and showed clinical activity, with three partial responses and 19 disease stabilizations. Results of a third randomized phase II trial of concurrent administration of temozolomide and radiation therapy followed by adjuvant temozolomide therapy compared with radiation alone showed a higher rate of complete and partial responses (objective response of 96% v 67%) and significantly more complete responses (38% v 33%, P =.017), primarily in patients with newly diagnosed brain and lung metastases.
Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. [2021]Label="BACKGROUND">Temozolomide is an alkylating agent approved by the U.S. Food and Drug Administration in 1999 for the treatment of patients with primary brain tumors. The aim of this study was to confirm the bioequivalence and safety of two strengths (20-100 mg) of generic temozolomide in the form of TOZ039 and Temodal® capsules administered to brain tumor patients.
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.
Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. [2022]Temozolomide (TMZ) is a newly approved alkylating agent for the treatment of malignant gliomas. To investigate resistance mechanisms in a multidrug therapeutic approach, a TMZ-resistant human glioma cell line, SF188/TR, was established by stepwise exposure of human SF188 parental cells to TMZ for approximately 6 months. SF188/TR showed 6-fold resistance to TMZ and cross-resistance to a broad spectrum of other anticancer agents that included 3-5-fold resistance to melphalan (MEL), gemcitabine (GEM), paclitaxel (PAC), methotrexate (MTX), and doxorubicin (DOX), and 1.6-2-fold resistance to cisplatin (CDDP) and topotecan (TPT). Alkylguanine alkyltransferase (AGT) activity was increased significantly in the resistant cell line compared with the parental cell line (P
Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. [2018]Temozolomide plus thalidomide is a promising oral combination regimen for the treatment of metastatic melanoma. The current Phase II study examined the efficacy and safety of this combination in chemotherapy-naive patients with brain metastases.
Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. [2018]A combination regimen of temozolomide (TMZ) and pegylated liposomal doxorubicin has been evaluated in the treatment of brain metastases from solid tumours.