HUMC 1612: Optune NovoTTF-200A System

• Status: Recruiting
• Trial end date: 2019-02-01
• Target enrollment: 12
• Participant gender: All

Summary

The purpose of this study is to determine if the Optune NovoTTF-200A device can be safely used in pediatric patients with high-grade glioma, both alone and in combination with standard chemotherapy medications.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hackensack Meridian Health
• Collaborator: NovoCure Ltd.
• Treatments: Alkylating Agents; Bevacizumab; Dacarbazine; Temozolomide

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 (either WHO Grade III anaplastic astrocytoma or WHO Grade IV glioblastoma multiforme). Patients in the initial cohort must have a tumor that is progressive or recurrent to standard chemotherapy. Patients in the second cohort may be newly diagnosed or have a tumor that is progressive, recurrent, or refractory to standard chemotherapy.

• 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.

• Recurrent high-grade glioma patients must begin therapy within four weeks of documented tumor progression by MRI scan. 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.

• 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).

Additional Inclusion criteria for Cohort 2 (Optune NovoTTF-200A + chemotherapy) only:

• 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.

Exclusion Criteria:

• Head circumference < 44 cm

• Infra-tentorial 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)

• 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

Additional Exclusion criteria for Cohort 2 (Optune NovoTTF-200A + chemotherapy) only:

• Prior therapy with temozolomide and/or bevacizumab. The lone exception to this rule is temozolomide and/or bevacizumab administered solely during radiation therapy.

• Known hypersensitivity to temozolomide or bevacizumab

• Patients who are unable to take oral medications because of significant uncontrolled vomiting

• Patients with 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 with known clinically significant bleeding diathesis or coagulopathy

• Patients who have experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents

• Patients previously diagnosed with deep venous thrombosis (including pulmonary embolism), and 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).

• 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.

• History of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies