HUMC 1612: Optune NovoTTF-200A System

• ClinicalTrials.gov Identifier: NCT03128047
• Recruitment Status: Active, not recruiting
• First Posted: April 25, 2017
• Last Update Posted: May 14, 2024
• Sponsor: Hackensack Meridian Health
• Collaborator: NovoCure Ltd.
• Information provided by (Responsible Party): Hackensack Meridian Health

Tracking Information

• First Submitted Date: January 5, 2017
• First Posted Date: April 25, 2017
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: April 6, 2017
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2019)

• Safety of the Optune NovoTTF-200A System when used alone in pediatric patients with recurrent high-grade gliomas. [ Time Frame: 56 Days ]
  Number of participants receiving treatment with the Optune NovoTTF-200A System with treatment-related adverse events as assessed by CTCAE v4.0.
• Tolerability of the Optune NovoTTF-200A System when used alone in pediatric patients with recurrent high-grade gliomas. [ Time Frame: 56 Days ]
  Number of participants receiving treatment with the Optune NovoTTF-200A System with who return tolerability questionaire

Original Primary Outcome Measures (submitted: April 20, 2017)

• Safety and tolerability of the Optune NovoTTF-200A System when used alone in pediatric patients with recurrent high-grade gliomas. [ Time Frame: 56 Days ]
  Number of participants receiving treatment with the Optune NovoTTF-200A System with treatment-related adverse events as assessed by CTCAE v4.0.
• Safety and tolerability of the Optune NovoTTF-200A System when used in combination with temozolomide and bevacizumab in pediatric patients with newly diagnosed or recurrent high-grade gliomas. [ Time Frame: 56 Days ]
  Number of participants receiving treatment with the Optune NovoTTF-200A System in combination with temozolomide and bevacizumab with treatment-related adverse events as assessed by CTCAE v4.0.

Current Secondary Outcome Measures (submitted: May 14, 2019)

• Assess the progression free of patients treated on this study protocol to aid in the future development of pediatric phase II/III studies using the Optune NovoTTF-200A System. [ Time Frame: Up to 2 years after study entry ]
  Number of events
• Assess the overall survival of patients treated on this study protocol to aid in the future development of pediatric phase II/III studies using the Optune NovoTTF-200A System. [ Time Frame: Up to 2 years after study entry ]
  Number of events

Original Secondary Outcome Measures (submitted: April 20, 2017)

• Assess the event-free and overall survival of patients treated on this study protocol to aid in the future development of pediatric phase II/III studies using the Optune NovoTTF-200A System. [ Time Frame: Up to 2 years after study entry ]
  Number of events
• Survival of patients with recurrent high-grade glioma receiving treatment with the Optune NovoTTF-200A System. [ Time Frame: Up to 2 years after study entry ]
  Assess the survival time
• 2-year event-free survival (EFS) and overall survival (OS) of patients with recurrent high-grade glioma treated with the Optune NovoTTF-200A System monotherapy and in combination with temozolomide and bevacizumab [ Time Frame: Up to 2 years after study entry ]
  Collect number of events and survival time
• Survival of patients with high-grade glioma receiving treatment with the Optune NovoTTF-200A System in combination with temozolomide and bevacizumab [ Time Frame: Up to 2 years after study entry ]
  Assess survival time

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: HUMC 1612: Optune NovoTTF-200A System
• Official Title: HUMC 1612: A Phase I Trial of the Optune NovoTTF-200A System With Concomitant Temozolomide and Bevacizumab in Pediatric Patients With High-grade Glioma
• Brief Summary: The purpose of this study is to determine if the Optune NovoTTF-200A device can be safely used in combination with chemotherapy in pediatric patients with recurrent high-grade glioma and ependemoma.

Detailed Description

This phase I trial will utilize a standard 3+3 design to determine the safety and tolerability of the Optune NovoTTF-200A System in pediatric patients with recurrent high-grade glioma end ependemomas.

Patients will receive treatment with the Optune NovoTTF-200A System along with Temozolomide and Bevacizumab and will consist of children with recurrent high-grade gliomas and Ependamomas. Patients enrolled will receive treatment with the Optune NovoTTF-200A with 200kHz for a minimum of 18 hours per day in 28 day cycles as monotherapy. Phase I safety evaluation will take place over the initial two cycles (56 days) of treatment. Following the completion of the safety evaluation period, patients will continue to receive treatment in 28 day cycles, which may be repeated continuously without therapy interruption for 12 cycles or until clinical criteria for discontinuation are met. Patients how appear to benefit from this treatment may be allowed to continue treatment beyond 12 cycles if approved by the study Principle Investigator.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• High Grade Glioma
• Ependymoma

Intervention

Device: Optune NovoTTF-200A System

Optune NovoTTF-200A System receive treatment with 200kHz for a minimum of 18 hours per day in 28 day cycles combined with Temozolomide and Bevacizumab.

Study Arms

Experimental: Recurrent high grade gliomas and ependymomas

Recurrent high-grade glioma and ependamoma patients will receive treatment with the Optune NovoTTF-200A system as monotherapy.

Interventions: Device: Optune NovoTTF-200A System Optune NovoTTF-200A System receive treatment with 200kHz for a minimum of 18 hours per day in 28 day cycles combined with Temozolomide and Bevacizumab.

Intervention: Device: Optune NovoTTF-200A System

Publications *

• Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
• Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
• Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.
• Chaudhry A, Benson L, Varshaver M, Farber O, Weinberg U, Kirson E, Palti Y. NovoTTF-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL system user study. World J Surg Oncol. 2015 Nov 11;13:316. doi: 10.1186/s12957-015-0722-3.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 3, 2019): 6
• Original Estimated Enrollment (submitted: April 20, 2017): 12
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have a minimum head circumference of 44 cm
• Patients must have a histologically- or cytologically-confirmed supratentorial high-grade glioma or supratentorial ependemoma.
• Patients with metastatic disease involving the infratentorium or spinal cord are eligible providing that they have a supratentorial tumor that is able to be targeted with TTFields.
• Eligible pathologic diagnoses include:

High-grade Glioma (WHO Grade III or IV): Anaplastic Astrocytoma, Astroblastoma, Diffuse Midline Glioma, Glioblastoma, Gliosarcoma Ependymoma (WHO Grade II or III):Ependymoma, Anaplastic Ependymoma

• Patients with high-grade glioma must must have be newly-diagnosed or have a tumor that is progressive or recurrent following standard treatment. Patients with ependymoma must have a tumor that is progressive or recurrent following standard treatment.
• Patients must have received the maximal feasible resection of their tumor and radiation therapy (unless contraindicated due to patient age) as part of their initial treatment prior to study enrollment.
• Patients must be enrolled before treatment begins. Treatment must start within 14 days of study enrollment.
• All clinical and laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated in the eligibility section.
• Newly-diagnosed patients must begin therapy within six weeks of the completion of radiotherapy, or within six weeks of surgical resection if radiotherapy is contraindicated.
• Recurrent high-grade glioma patients must begin therapy within four weeks of documented tumor progression by MRI scan.
• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
• Able to undergo adequate tumor imaging, via magnetic resonance imaging (MRI) scan to evaluate disease evolution.
• Adequate hematologic, renal, liver function as demonstrated by laboratory values: ANC ≥ 1,000/ul Hemoglobin ≥8.0 gm/dl Platelet count ≥ 100,000/ul

Adequate Liver Function Defined As:

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age. Adequate Renal Function Defined As Either
• Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2

• or a serum creatinine less than or equal to the institutional normal for age

  • Negative pregnancy test in women of childbearing potential within 7 days of initiating investigational therapy
  • Recent mothers must agree not to breast feed while receiving medications on study
  • Patient or legal guardian must give written, informed consent or assent (when applicable).
  • Able to swallow and ingest oral medication or have a NG or G-tube for drug administration
  • Urine protein should be screened by urine analysis. If protein ≥ 2+ on urinalysis, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.

Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1000 mg. UPC ratio is calculated using one of the following formula:

• [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL
• [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
• Adequate Coagulation Defined As: PT/INR ≤ 1.5 x upper limit of normal

Exclusion Criteria:

• Age less than 5 or greater than or equal to 18 years
• Head circumference < 44 cm
• Absence of supratentorial tumor
• Use of any other investigational drug within five half-lives of that drug prior to the initiation of protocol therapy
• Anti-cancer therapy within 4 weeks prior to the initiation of protocol therapy (6 weeks for mitomycin and nitrosureas, 4 weeks for curative-intent radiotherapy, and 2 weeks for palliative radiotherapy)
• Any National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE version 4.0) >Grade 1 toxicities from prior chemotherapy or radiotherapy that could impact on safety outcome assessment
• Any surgery within 14 days prior to initiation of protocol therapy (excluding shunt or line insertion)
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness) Patients receiving escalating doses of corticosteroids to control symptoms of increased intracranial pressure (e.g., require a stable or decreasing dose of corticosteroids for at least 7 days prior to enrollment) will also be excluded.
• Known > Grade 1 intracranial or intratumoral hemorrhage either by CT or MRI scan within the last 1 month. Patients with resolving hemorrhage changes, punctuate hemorrhage or hemosiderin may enter the study
• Pregnant female patients, Pregnancy tests with a negative result must be obtained in all post-menarchal females.
• Lactating females must agree they will not breastfeed a child while on this study.
• Males and females of reproductive potential may not participate unless they agree to use an effective contraceptive method and continue to do so for at least 6 months after the completion of therapy.
• Any serious and/or unstable pre-existing medical, psychiatric or other condition which in the Investigator's opinion could interfere with subject safety, obtaining written informed consent, or compliance with the study protocol
• Known hypersensitivity to temozolomide or bevacizumab
• Patients who are unable to take oral medications because of significant uncontrolled vomiting will be excluded.
• Patients must not have a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, Grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia.
• Patients must not have a known clinically significant bleeding diathesis or coagulopathy
• Patients who have experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents are excluded from participation.
• Patients must not have been previously diagnosed with a deep venous thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition (e.g., protein S, protein C, antithrombin III deficiency, Factor V Leiden or Factor II G202'0A mutation, homocysteinemia, or antiphospholipid antibody syndrome).
• Patients must not have a history of an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 6 months prior to study entry.
• Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study.
• Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies are ineligible.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03128047
• Other Study ID Numbers: Pro2016-0583
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hackensack Meridian Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Hackensack Meridian Health
• Original Study Sponsor: Same as current
• Collaborators: NovoCure Ltd.

Investigators

• Principal Investigator: Derek Hanson, MD; Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center

• PRS Account: Hackensack Meridian Health
• Verification Date: May 2024