Study Of NOVOTTF-200A In Bevacizumab-Naive Subjects With Recurrent Grade III Malignant Astrocytoma

Phase II, Single Arm Study Of NOVOTTF-200A In Bevacizumab-Naive Subjects With Recurrent WHO Grade III Malignant Astrocytoma

This is a Phase 2 study in subjects with WHO Grade III Anaplastic Astrocytoma (G3 astrocytoma) who had progressive disease during first or second line treatment and who have not previously received any BEV or any experimental agents.

Study Overview

• Status: Completed
• Conditions: Astrocytoma, Grade III
• Intervention / Treatment: Device: NOVOTTF-200A

Detailed Description

Primary Objective:

The primary objective will be to determine the efficacy of NOVOTTF-200A in recurrent anaplastic astrocytoma patients (6-month progression-free survival)

Secondary Objectives:

• To evaluate the safety of NOVOTTF-200A in the subject population.
• To evaluate efficacy of NOVOTTF-200A in the subject population.
• To see if the presence of ATRX, TERT promoter, IDH1 mutations and/or MGMT promoter methylation, confers a better response to NOVOTTF-200A.

• To determine if the treatment significantly modifies the patient's quality of life. Sponsor will use the Functional Assessment of Cancer Therapy (FACT) questionnaires:

  • FACT-Brain (FACT-Br)
  • FACT-Cognitive Function (FACT-Cog)

Exploratory Objectives:

• To determine if the presence of proneural or mesenchymal phenotype (Cytoscan analysis) confers a better response to NovoTTF.
• To determine if the in vitro sensitivity of the glioma cells derived from patient specimens before and after the NOVOTTF-200A treatment correlates with the patient's response to treatment.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Understand and voluntarily sign and date an informed consent document before any study related assessments/procedures are conducted.
2. Males and females of age ≥18 years at the time of the signing of the informed consent document.
3. All subjects must have histologic evidence of G3 MG and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bi-dimensional product of enhancement, a new enhancing lesion or a significant increase in T2 FLAIR).
4. Subjects with archival tumor tissue suitable for genetic testing must give permission to access and test the tissue; subjects without archival tumor tissue are eligible.
5. No prior treatment with BEV or any anti-angiogenesis agents.
6. At least 4 weeks from surgical resection and 12 weeks from end of radiotherapy prior to enrollment in this study, unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are two MRIs confirming progressive disease that are 8 weeks apart.
7. All AEs resulting from prior chemotherapy, surgery or radiotherapy must have resolved to NCI-CTCAE (v. 4.03) Grade ≤1 (except for laboratory parameters outlined below).

8. Laboratory results within 7 days prior to NOVOTTF-200A administration (transfusions and/or growth factor support may be used at the discretion of the Investigator during Screening):

   • Hemoglobin ≥9 g/dL.
   • Absolute neutrophil count (ANC) ≥1.5 × 109/L.
   • Platelet count ≥100 × 109/L.
   • Serum bilirubin ≤1.5 × upper limit of normal (ULN) or ≤3 × ULN if Gilbert's disease is documented.
   • Aspartate transaminase (AST) ≤ 2.5 ULN.
   • Serum creatinine ≤1.5 × ULN.
9. Karnofsky Performance Status (KPS) score ≥70%.
10. Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. The presence of 1p19q LOH which is diagnostic for anaplastic oligodendroglioma (AO).
2. Co-medication that may interfere with study results, e.g., immunosuppressive agents other than corticosteroids. (Steroid therapy for control of cerebral edema is allowed at the discretion of the investigator. Subjects should be on a stable dose of steroids for at least 1 week prior to study beginning.)
3. Chemotherapy administered within 4 weeks (6 weeks for an IV nitrosoureas and 12 weeks for an implanted nitrosoureas wafer) prior to Day 1 of study treatment.
4. Pregnancy or breastfeeding.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit adherence with study requirements, or disorders associated with significant immunocompromised state.
6. Known previous/current malignancy requiring treatment within ≤ 3 years except for cervical carcinoma in situ, squamous or basal cell skin carcinoma and superficial bladder carcinoma.
7. Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator.

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
Other: NOVOTTF-200A; NOVOTTF-200A treatment in Bevacizumab-Naïve Subjects with Recurrent WHO Grade III Malignant Astrocytoma	Device: NOVOTTF-200A; NOVOTTF-200A will be administered under appropriate guidelines. Monthly adherence rate >= 75% (>= 18 hours/day) over a 4-week cycle (28 days) will be strongly encouraged.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Showing no Evidence of Disease Progression Six Months After Initiating Treatment With the Device.	The primary objective is to estimate the proportion of participants showing no evidence of disease progression six months after initiating treatment with the device. Assessment is per RANO (2010) criteria.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience Any Adverse Events Who Received NOVOTTF-200A.	All subjects will be evaluated for safety analysis if they receive NOVOTTF-200A. Safety and tolerability of NOVOTTF-200A treatment will be based on the incidence and severity of adverse events and toxicities. Toxicities will be assessed according to the "Common toxicity criteria (CTC), version 4.03". Refer to the Adverse Events (AEs) section for full list of reported AEs.	1 year
Does the Treatment Significantly Modify the Patient's Quality of Life?	To determine if the treatment significantly modifies the patient's quality of life we will be using the Functional Assessment of Cancer Therapy (FACT) questionnaires that include the FACT-Brain (FACT-Br), and the FACT-Cognitive Function (FACT-Cog) questionnaires. These will be completed at baseline then every two cycles. Scores of FACT-COG and FACT-Br are combined below at baseline and last cycle of treatment. Scores of FACT-COG and FACT-Br are summed to obtain a total possible scale range of 0 to 272. FACT-Cog (using the Cognitive Impairments subscale) with a score range from 0-72 and FACT-Br with a score range from 0-200. A higher score, means a better quality of life.	Will be assessed at baseline and every two cycles (at the end of each even-numbered cycle of therapy) until treatment termination, an average of 24 months
Correlations With Established Molecular Markers (ATRX, and/or Mutation and MGMT Promoter Methylation	To see if the presence of ATRX, TERT promoter, IDH1 mutations and/or MGMT promoter methylation, confers a better response to NOVOTTF-200A.	Assessed at screening.

Collaborators and Investigators

• Sponsor: Daniela A. Bota
• Collaborators: NovoCure Ltd.
• Investigators: Principal Investigator: Daniela Bota, MD, UC Irvine Health

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Actual): September 7, 2023
• Study Completion (Actual): August 7, 2025

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Astrocytoma
• Other Study ID Numbers: 20174031; UCI 16-56 (Other Identifier: UCI CFCCC)

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.: No