Temozolomide, Radiation Therapy, and Tumor Treating Fields Therapy in Treating Participants With Glioblastoma

SPARE-Scalp Preservation and Radiation Plus Alternating Electric Tumor Treatment Field (NovoTTF, Optune) for Patients With Glioblastoma: A Pilot Study

This pilot early phase I trial studies the side effects of temozolomide, radiation therapy, and tumor treating fields therapy using Novo tumor treatment fields (TTF)-200A device in participants with glioblastoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. NovoTTF-200A device is a portable device that produces alternating electrical fields that may disrupt growth of cancer cells. Giving temozolomide, radiation therapy, and tumor treating fields therapy using NovoTTF-200A device may work better in treating participants with glioblastoma.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Temozolomide; Device: NovoTTF-200A Device; Procedure: Tumor Treating Fields Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity of combination chemoradiotherapy with NovoTTF-200A device (Optune) treatment in newly diagnosed glioblastoma.

SECONDARY OBJECTIVES:

I. To determine the median progression-free survival of patients with newly diagnosed glioblastoma treated with radiotherapy with concurrent and adjuvant temozolomide plus Optune.

II. To evaluate the median overall survival, 1-year overall survival, and event-free survival.

III. Collect tumor O(6)-Methylguanine-DNA-methyltransferase (MGMT) methylation status and isocitrate dehydrogenase (IDH) mutation status.

IV. To evaluate the level of circulating tumor deoxyribonucleic acid (DNA) in glioblastoma patient serum during treatment.

V. To evaluate the quality of life of patients treated with radiotherapy with concurrent and adjuvant temozolomide plus Optune.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with pathology confirmed newly diagnosed World Health Organization (WHO) grade IV glioma
• Karnofsky performance status (KPS) ≥ 60
• Patients must have recovered from the effects of surgery per treating physician's judgment; there must be a minimum of 21 days from the day of surgery to the day of protocol treatment; for core or needle biopsy, a minimum of 14 days must have elapsed prior to the day of protocol treatment
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3
• Platelets ≥ 100,000 cells/mm^3
• Hemoglobin ≥ 9.0 g/dl
• Creatinine clearance > 30 mL/min
• Bilirubin < 2.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of normal range
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 4 months after last dose of temozolomide
• Is able to have magnetic resonance imaging (MRI) with contrast of the brain
• All subjects must be able to comprehend and sign a written informed consent document. If the subject can comprehend the informed consent but is unable to sign, a LAR may sign the written informed consent document.

Exclusion Criteria:

• Infratentorial disease (defined as glioblastoma [GBM] derived from cerebellum or brainstem)
• Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias
• A skull defect (such as, missing bone with no replacement)
• Women of childbearing potential who are pregnant or breastfeeding
• Evidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema)
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study, in the opinion of the investigator
• Prior radiation treatment to the brain
• Prior treatment with temozolomide
• Known hypersensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
• Known active collagen vascular disease

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: Treatment (temozolomide, radiation, NovoTTF-200A device); Participants receive temozolomide PO QD starting day 1 to the end of radiation therapy and undergo 30 fractions of radiation therapy over 15-20 minutes each, 5 days a week (Monday-Friday) for 6 weeks. Beginning day 1 of radiation therapy, participants undergo tumor treatment fields therapy using NovoTTF-200A device over 18 hours or more daily in the absence of disease progression or unacceptable toxicity. Beginning 28 days after the last dose of radiation therapy, participants receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; Irradiate; RT; Drug: Temozolomide; Given PO; Other Names: Temodar; Temodal; Temcad; Methazolastone; 362856; Device: NovoTTF-200A Device; Undergo tumor treatment fields therapy using NovoTTF-200A device; Other Names: Optune; Procedure: Tumor Treating Fields Therapy; Undergo tumor treatment fields therapy using NovoTTF-200A device; Other Names: Alternating Electric Field Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NovoTTF-200A device discontinuation rate due to skin toxicity	Discontinuation events are defined as the discontinuation of NovoTTF-200A device for > 7 consecutive days due to skin toxicity of grade 3 or higher. For discontinuation rates, the method of Atkinson and Brown will be used to allow for the two-stage design. Descriptive analysis will be performed on the acute toxicity data.	Up to 30 days after finishing chemoradiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Will be evaluated using the Kaplan-Meier method.	From enrollment up to 1 year
Overall survival	Will be evaluated using the Kaplan-Meier method.	From enrollment up to 1 year
Event-free survival	Will be evaluated using the Kaplan-Meier method.	From enrollment up to 1 year

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: NovoCure Ltd.
• Investigators: Principal Investigator: Wenyin Shi, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

General Publications

• Miller R, Song A, Ali A, Niazi M, Bar-Ad V, Martinez N, Glass J, Alnahhas I, Andrews D, Judy K, Evans J, Farrell C, Werner-Wasik M, Chervoneva I, Ly M, Palmer J, Liu H, Shi W. Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma. Front Oncol. 2022 Apr 29;12:896246. doi: 10.3389/fonc.2022.896246. eCollection 2022.
• Ali AS, Lombardo J, Niazi MZ, Miller RC, Alnahhas I, Martinez NL, Andrews DW, Judy KD, Shi W. Concurrent chemoradiation and Tumor Treating Fields (TTFields, 200 kHz) for patients with newly diagnosed glioblastoma: patterns of progression in a single institution pilot study. J Neurooncol. 2022 Nov;160(2):345-350. doi: 10.1007/s11060-022-04146-w. Epub 2022 Nov 10.
• Song A, Bar-Ad V, Martinez N, Glass J, Andrews DW, Judy K, Evans JJ, Farrell CJ, Werner-Wasik M, Chervoneva I, Ly M, Palmer JD, Liu H, Shi W. Initial experience with scalp sparing radiation with concurrent temozolomide and tumor treatment fields (SPARE) for patients with newly diagnosed glioblastoma. J Neurooncol. 2020 May;147(3):653-661. doi: 10.1007/s11060-020-03466-z. Epub 2020 Mar 23.

Helpful Links

• Thomas Jefferson University Hospital
• Sidney Kimmel Cancer Center at Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2018
• Primary Completion (Actual): April 21, 2021
• Study Completion (Actual): January 26, 2024

Study Registration Dates

• First Submitted: March 19, 2018
• First Submitted That Met QC Criteria: March 19, 2018
• First Posted (Actual): March 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 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; Temozolomide
• Other Study ID Numbers: 17P.346

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes