TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma

NCT02663271 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB201600074OCR14874
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Glioblastoma multiforme (GBM) is the most common and deadliest primary malignant neoplasm of the central nervous system in adults. Despite an aggressive multimodality treatment approach including surgery, radiation therapy and chemotherapy, overall survival remains poor. Novocure has shown that when properly tuned, very low intensity, intermediate frequency electric fields (TTFields) stunt the growth of tumor cells. The Optune system (NovoTTFTM Therapy) is a portable battery operated device, which produces TTFields within the human body by means of surface transducer arrays. The TTFields are applied to the patient by means of surface transducer arrays that are electrically insulated, so that resistively coupled electric currents are not delivered to the patient. Optune is currently FDA-approved as a single modality treatment for recurrent GBM when both surgical and radiotherapy options have been exhausted as well as combination with adjuvant temozolomide for newly diagnosed GBM. This research study is being performed to determine whether or not TTFields combined with pulsed bevacizumab treatment increases overall survival in patients with bevacizumab-refractory GBM compared to historical controls treated with continuous bevacizumab alone or in combination with other chemotherapy.

Conditions

Glioblastoma Multiforme; Glioblastoma; Malignant Glioma; GBM

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.

  from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months

Secondary Outcomes (3)

• Karnofsky Performance Scale

  Assessed up to 24 months

• Mini-Mental Status Exam

  Assessed up to 24 months

• Response Assessment in Neuro-Oncology (RANO) Measurement Form

  Assessed up to 24 months

Study Arms (1)

Optune+Pulsed Bevacizumab

EXPERIMENTAL

The subjects will undergo 12 months of planned continuous treatment with Optune. The treatment will begin at week 0 and will be continuous throughout the study. Pulsed bevacizumab dosing is defined by at least one cycle on and at least one cycle off. A cycle is defined as 8 weeks in length. If after one cycle on, there is no evidence of a repeat response; bevacizumab will be continued for one more cycle. If after two cycles on, there is no repeat response; bevacizumab will be continued with or without other standard chemotherapy until death. If after at least one cycle on, there is evidence of repeat response, bevacizumab will be discontinued for at least one cycle. In addition, the following will be performed: Bevacizumab will be given, physical examination and quality of life questionnaires will be performed and brain MRI.

Drug: Bevacizumab; Device: Optune; Other: Brain MRI; Other: Quality of Life Questionnaires

Interventions

Bevacizumab DRUG

Bevacizumab will be given at 10mg/kg IV every 2 weeks.

Also known as: Avastin

Optune+Pulsed Bevacizumab

Optune DEVICE

Optune will be worn continuously for 12 months. Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS. There will be no adjustments made to the device by investigators or patients/caregivers.

Also known as: NovoTTF™-100A System

Optune+Pulsed Bevacizumab

Brain MRI OTHER

Brain MRI will be done at screening and every 8 weeks.

Also known as: Magnetic resonance imaging

Optune+Pulsed Bevacizumab

Quality of Life Questionnaires OTHER

The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.

Also known as: Karnofsky Performance Scale, MMSE

Optune+Pulsed Bevacizumab

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed GBM, WHO grade IV. GBM variants and secondary GBM are allowed in any recurrence (including multiple) and have been treated with radiation and chemotherapy.
• Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.
• Patient is a candidate for, and agrees to proceed with additional bevacizumab treatment.
• Male or female at least 22 years of age or older.
• Karnofsky Performance Scale (KPS) ≥ 60%.
• Planned treatment with TTFields therapy.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of treatment.
• Participants of childbearing/reproductive potential must use effective contraception.
• Participants must be able to understand and willing to comply with protocol requirements as assessed by the investigator.
• Signed informed consent according to institutional guidelines prior to registration.

You may not qualify if:

• Inability to undergo brain MRI due to medical or personal reasons.
• Currently receiving investigational agents that are intended as treatments of recurrent GBM.
• Skull defect such as missing bone or bullet fragments.
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, heart attack within the previous 12 months, stroke (except for TIA) within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
• Intracranial hemorrhage except for tumor associated micro hemorrhage.
• Women who are pregnant or breastfeeding.
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, vagus nerve stimulator, and other implanted electronic devices in the brain or the spinal cord.
• Tumor located entirely in the infratentorium.
• History of hypersensitivity to hydrogel.

Sponsors & Collaborators

• University of Florida: lead
• NovoCure Ltd.: collaborator

Study Sites (2)

University of Florida

Gainesville, Florida, 32611, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Bevacizumab; Magnetic Resonance Spectroscopy; Karnofsky Performance Status

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Severity of Illness Index; Patient Acuity; Health Status Indicators; Health Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: David Tran, MD, PhD
• Organization: University of Florida

david.tran@neurosurgery.ufl.edu

352-273-9000

Study Officials

• David D Tran, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: January 26, 2016
• Study Start: December 19, 2016
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: June 23, 2022
• Results First Posted: June 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)