TTField in Combination With Temozolomide and Tislelizumab in The Treatment of Newly Diagnosed Glioblastoma.

Tumor-Treating Fields (TTFields) in Combination With Temozolomide and Tislelizumab in The Treatment of Newly Diagnosed Glioblastoma: A Safety and Efficacy Clinical Study

The goal of this clinical trial is To investigate the safety and efficacy of Tumor-Treating Fields (TTFields) in combined with temozolomide (TMZ) and tislelizumab in the treatment of newly diagnosed glioblastoma (GBM).

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Tislelizumab; Device: Tumor Treating Fields; Drug: Temozolomide (TMZ)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Huashan Hospital Affiliated to Fudan University
    • Contact: Liang Chen; Phone Number: +86 21 5460 1999; Email: chenlianghs@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. After brain surgery (patients with total resection, partial resection and biopsy were acceptable), the pathological examination confirmed glioblastoma with isocitrate dehydrogenase (IDH) wild-type according to the 2021 World Health Organization (WHO) classification of tumors of the central nervous system.
2. The age of the subjects was ≥18 years old;
3. Supratentorial tumors;
4. Patients who had undergone maximal surgical resection (biopsy) and completed TMZ concurrent chemoradiotherapy were planned for adjuvant TMZ treatment.
5. Karnofsky performance status (KPS) score ≥70;
6. The predicted survival time was ≥3 months.
7. Voluntarily signed informed consent;
8. Subjects of childbearing potential had to agree to use effective contraception for the duration of the trial.

Exclusion Criteria:

1. Early progression of GBM occurred after TMZ+radiation therapy (RT) treatment (except pseudoprogression, imaging examination should be supplemented to further exclude if necessary).
2. The subject had received any other cytotoxic or biologic antineoplastic therapy before enrollment;
3. Distant leptomeningeal metastasis;
4. Patients had a diagnosis of cancer other than glioblastoma and received antineoplastic therapy within 5 years before enrollment, excluding cured stage I prostate cancer, cervical or uterine cancer in situ, breast cancer in situ, and nonmelanoma skin cancer.
5. Previous treatment with anti-PD-1 antibody/anti-PD-L1 antibody and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody;
6. Participants who had received systemic immunosuppressive therapy (including but not limited to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, thalidomide, or antineoplastic factor agents) within 2 weeks before enrollment. Excluding nasal sprays and inhaled corticosteroids;
7. The presence of an active, known, or suspected autoimmune disease that was judged by the investigator to be unsuitable for this study. The following exclusions may be made: vitiligo, alopecia, Graves' disease, psoriasis, or eczema that did not require systemic treatment within the previous 2 years; Hypothyroidism (due to autoimmune thyroiditis) that is asymptomatic or requires only stable doses of hormone-replacement therapy or type I diabetes that requires only stable doses of insulin-replacement therapy, or childhood asthma that has resolved completely without intervention or recurrence in adulthood without an external trigger.

8. Participants had to meet certain criteria for bone marrow, liver and kidney function before enrollment, and were not eligible if they had any of the following:

   1. Thrombocytopenia (platelet count < 100×103/μL)
   2. Neutropenia (absolute neutrophil count < 1.5×103/μL)
   3. National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) 4 grade non-hematologic toxicity (except alopecia, nausea and vomiting)
   4. Significant liver function impairment -aspartate aminotransferase (AST) or alanine transaminase (ALT) exceeding 3 times the upper limit of normal
   5. Total bilirubin more than 1.5 times the upper limit of the normal range
   6. Severe renal impairment (serum creatinine >1.7 mg/dL, or >150 μmol/L).
9. The subject had an active implanted device (deep brain stimulator, spinal cord stimulator, vagus nerve stimulator, pacemaker, cardiac defibrillator, etc.).
10. Infratentorial tumors;
11. Documented increased intracranial pressure (clinically manifested as severe papilledema, vomiting, nausea, or decreased consciousness);
12. There were infection, ulcer and unhealed wound in the skin where the electrode was applied.
13. A known history of allergy to TMZ or tislelizumab;
14. Skull defects or residual metal fragments in the skull (except titanium plates or nails used for skull surgery);
15. Patients allergic to conductive hydrogels or medical adhesives;
16. Those who are pregnant or preparing to become pregnant or who are breastfeeding;
17. Patients with poor compliance, as judged by the investigator, or other factors considered by the investigator to be not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tumor Treating Fields + Temozolomide + Tislelizumab

Drug: Tislelizumab; Tislelizumab will be given 300 mg intravenously every 4 weeks beginning on Day 1 of Cycle 2 of adjuvant TMZ. The Tislelizumab treatment should be continued until confirmed PD, unacceptable toxicity, or finished Tislelizumab treatment for other reasons.; Device: Tumor Treating Fields; Tumor Treating Fields will be administered continuously with a planned ≥ 18 h per day, starting on the Day 1 of cycle 1 (C1D1), throughout the entire course of treatment.; Drug: Temozolomide (TMZ); The patients will carry out 6 cycles of TMZ adjuvant chemotherapy according to the instructions. The dosage of TMZ is 150-200 mg/(m2·d), daily for 5 days followed by 23 days without treatment, the treatment cycle is 28 days. The initial dose of cycle 1 is 150 mg/(m2·d), if patients do not experience TMZ chemotherapy toxicity, the dose should be increased to 200 mg/(m2·d) in subsequent treatment cycles. After 6 cycles of TMZ adjuvant chemotherapy, if the patients do not experience disease progression, it is recommended to continue TMZ adjuvant chemotherapy, or treated according to investigators' recommendations. The TMZ treatment should be continued until confirmed progressive disease (PD), unacceptable toxicity, or finished TMZ treatment for other reasons.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from the start of treatment until disease progression or death due to any cause, whichever occurs first	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Adverse events will be defined as the incidence, frequency and severity of adverse events (AEs) noted in patients treated with study treatments	Up to 18 months
Overall Survival (OS)	OS is defined as the time from the date of treatment until death due to any cause	Up to 18 months
PFS rate at 6 months	The analysis will be estimated proportions of patients who are progression-free at 6 months following the time of enrollment	Up to 6 months
PFS rate at 1 year	The analysis will be estimated proportions of patients who are progression-free at 1 year following the time of enrollment	Up to12 months
OS rate at 1-year	The analysis will be estimated proportions of patients who are survival at 1 year following the time of enrollment	Up to12 months
Objective response rate (ORR)	ORR is defined as the number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR).	Up to 18 months
Disease control rate (DCR)	DCR is defined as the rate of best objective response of CR, PR, or stable disease (SD)	Up to 18 months

Collaborators and Investigators

• Sponsor: Jiangsu Healthy Life Innovation Medical Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2024
• Primary Completion (Estimated): July 15, 2025
• Study Completion (Estimated): March 9, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Temozolomide; Tislelizumab
• Other Study ID Numbers: HL-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No