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TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma

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ClinicalTrials.gov Identifier: NCT02663271
Recruitment Status : Recruiting
First Posted : January 26, 2016
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
NovoCure Ltd.
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE January 21, 2016
First Posted Date  ICMJE January 26, 2016
Last Update Posted Date March 14, 2019
Study Start Date  ICMJE August 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
Progression-free survival between the groups [ Time Frame: Assessed up to 24 months ]
Survival times in both the historical control group and the experimental group are assumed to follow Weibull distributions. Weibull-distributed survival times, the hazard ratio (experimental vs control) is equal to the ratio of the control group median survival time (m1) to the experimental group median survival time (m2), raised to the power of the shape parameter k: HR = (m1/m2)k
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02663271 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
  • Number of adverse events [ Time Frame: Change from baseline and every month up to 24 months ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting for grade 3 or higher.
  • Karnofsky Performance Scale [ Time Frame: Change from baseline and every month up to 24 months ]
    The Karnofsky Performance Scale is rated from 0 - 100 with 0 = death and 100 = normal without complaints or evidence of disease.
  • Mini-Mental Status Exam [ Time Frame: Change from baseline and every month up to 24 months ]
  • Response Assessment in Neuro-Oncology (RANO) Measurement Form [ Time Frame: Change from baseline and every 2 months up to 24 months ]
    Measurable lesions from the brain MRI must be contrast enhancing, have a minimum size of two perpendicular diameters > 10mm, no cavity or cyst in measurement. In addition, non-measurable lesions include lesions that are too small (<10 x 10mm), lesions that do not enhance, and lesions with a poorly defined margin. The lesions are measured with the sum of products of diameters (SPD).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
Official Title  ICMJE A Phase 2, Multi-center, Single Arm, Histologically Controlled Study Testing the Combination of TTFields and Pulsed Bevacizumab Treatment in Patients With Bevacizumab-refractory Recurrent Glioblastoma
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.

Detailed Description Subjects who have evidence of bevacizumab-refractory GBM will be eligible to participate in this research study. Subjects will undergo 12 months of planned continuous treatment with TTFields followed by pulsed bevacizumab treatment when there is evidence of further progression per RANO, with the option of extending treatment up to a total of 24 months in patients who have not progressed and/or have adequate performance status at the 12 month mark. 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 or until progression is noted again per RANO, whichever is later, at which time pulsed bevacizumab will be restarted as outlined above. The investigators believe that this approach will produce peaks and troughs in mitotic activities of glioma cells that render glioma cells more sensitive to the antimitotic activity of Optune during peak growth rates, thus lowering disease burden and increasing survival. In addition, the following will be performed: Bevacizumab will be given at 10mg/kg IV every 2 weeks. Physical examination and quality of life (QoL) assessments will be performed bi-monthly. Brain MRI will be performed every 2 months.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Glioblastoma
  • Malignant Glioma
  • GBM
Intervention  ICMJE
  • Drug: Bevacizumab
    Bevacizumab will be given at 10mg/kg IV every 2 weeks.
    Other Name: Avastin
  • Device: Optune
    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.
    Other Name: NovoTTF™-100A System
  • Other: Brain MRI
    Brain MRI will be done at screening and every 8 weeks.
    Other Name: Magnetic resonance imaging
  • Other: Quality of Life Questionnaires
    The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.
    Other Names:
    • Karnofsky Performance Scale
    • MMSE
Study Arms
  • Experimental: Optune+Pulsed Bevacizumab
    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.
    Interventions:
    • Drug: Bevacizumab
    • Device: Optune
    • Other: Brain MRI
    • Other: Quality of Life Questionnaires
  • Historical Controls
    Historical controls treated with continuous bevacizumab alone or in combination with standard chemotherapy will be compared with the Optune arm. Information will be collected: Bevacizumab or additional chemotherapy, physical examination and quality of life questionnaires performed and brain MRI.
    Interventions:
    • Drug: Bevacizumab
    • Other: Brain MRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2017)
18
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2016)
25
Estimated Study Completion Date March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 22 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02663271
Other Study ID Numbers  ICMJE IRB201600074
OCR14874 ( Other Identifier: University of Florida )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE NovoCure Ltd.
Investigators  ICMJE
Principal Investigator: David D Tran, MD, PhD University of Florida
PRS Account University of Florida
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP