Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM)

April 7, 2017 updated by: NovoCure Ltd.

A Prospective, Multi-center Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients With Newly Diagnosed GBM.

The study is a prospective, randomly controlled pivotal trial, designed to test the efficacy and safety of a medical device, the NovoTTF-100A, as an adjuvant to the best standard of care in the treatment of newly diagnosed GBM patients. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PAST CLINICAL EXPERIENCE:

The effect of the electric fields generated by the NovoTTF-100A device (TTFields, TTF) has been tested in a large prospective, randomized trial, in recurrent GBM. The outcome of subjects treated with the NovoTTF-100A device was compared to those treated with an effective best standard of care chemotherapy (including bevacizumab). NovoTTF-100A subjects had comparable overall survival to subjects receiving the best available chemotherapy in the US today. Similar results showing comparability of NovoTTF-100A to BSC chemotherapy were seen in all secondary endpoints.

Recurrent GBM patients treated with the NovoTTF-100A device in this trial experienced fewer side effects in general, significantly fewer treatment related side effects, and significantly lower gastrointestinal, hematological and infectious adverse events compared to controls. The only device-related adverse events seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality of life measures were better in NovoTTF-100A subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.

In a small scale pilot trial in newly diagnosed GBM patients, the treatment was well tolerated and suggested that NovoTTF-100A may improve time to disease progression and overall survival of newly diagnosed GBM patients. Although the number of patients in the pilot trial was small, The FDA has determined that the data gathered so far warrant testing of NovoTTF-100A treatment as a possible therapy for patients with newly diagnosed GBM.

DESCRIPTION OF THE TRIAL:

All patients included in this trial are newly diagnosed GBM patients who underwent a biopsy or surgery (with or without Gliadel wafers), followed by radiation therapy in combination with Temozolomide chemotherapy. In addition, all patients must meet all eligibility criteria.

Eligible patients will be randomly assigned to one of two groups:

  1. Treatment with the NovoTTF-100A device in combination with Temozolomide chemotherapy.
  2. Treatment with Temozolomide alone, as the best known standard of care.

Patients will be randomized at a 2:1 ratio (2 of every three patients who participate in the trial will be treated with the NovoTTF-100A device). Baseline tests will be performed in patients enrolled in both arms, including specific genetic tests done using tumor samples obtained during their initial surgery. If assigned to the NovoTTF-100A in combination with Temozolomide group, the patients will be treated continuously with the device until second progression. They will also receive temozolomide and possibly a second line treatment that can be one of the following: re-operation, local radiotherapy (gamma-knife), a second line of chemotherapy or a combination of the above.

NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays on the head. Electrode array placement will require shaving of the scalp before and frequently during the treatment. After an initial short visit to the clinic for training and monitoring, patients will be released to continue treatment at home where they can maintain their regular daily routine.

During the trial, regardless of which treatment group the patient was assigned to, he or she will need to return once every month to the clinic where an examination by a physician and a routine laboratory examinations will be done. These routine visits will continue for as long as the patient's disease is not progressing for the second time under the study treatment. If such occurs, patients will need to return once per month for two more months to the clinic for similar follow up examinations.

During the visits to the clinic patients will be examined physically and neurologically. Additionally, routine blood tests will be performed. A routine MRI of the head will be performed at baseline and every second month thereafter, until second progression. After this follow up plan, patients will be contacted once per month by telephone to answer basic questions about their health status.

SCIENTIFIC BACKGROUND:

Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet.

Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (200 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating.

The breakthrough finding made by NovoCure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause the building blocks of these cells to move and pile up in such a way that the cells physically explode. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields cause these tiny motors to fall apart since they have a special type of electric charge.

As a result of these two effects, cancer tumor growth is slowed and can even reverse after continuous exposure to TTFields.

Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach.

In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very few side effects and promising affectivity in slowing or reversing this disease.

Study Type

Interventional

Enrollment (Anticipated)

700

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria
        • University Hospital Graz
      • Vienna, Austria
        • Medical University of Vienna
      • Vienna, Austria
        • SMZ-Süd/Kaiser-Franz-Josef-Spital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Center
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Ontario
      • Hamilton,, Ontario, Canada, L8V5C2
        • Juravinski Cancer Centre
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H2L 4 M1
        • Notre-Dame Hospital (CHUM)
      • Montreal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute
      • Montreal, Quebec, Canada, H3T 1E2
        • McGill - Gerald Bronfman Centre for Clinical Research in Oncology -
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • (CHUS) Centre Hospitalier Universitaire de Sherbrooke, Service de Neurochirurgie
  • Czech Republic
      • Prague, Czech Republic
        • Na Homolce Hospital
  • France
      • Amiens, France
        • CHU Amiens Sud-Salouel
      • Angers, France
        • CHU Angers
      • Bordeaux, France
        • Hôpital Saint André Centre Hospitalier Universitaire (CHU) des Hôpitaux de Bordeaux
      • Lyon, France
        • Hospital of Neurology Pierre Wertheimer
      • Paris, France
        • Group Hospitals Pitie-Salpetriere
      • Toulouse, France
        • Centre Hospitalo-Universitaire de Toulouse Purpan
  • Germany
      • Hamburg, Germany
        • University Medical Center Hamburg-Eppendorf
      • Heidelberg, Germany
        • Medical University Heidelberg
      • Kiel, Germany
        • University Hospital of Schleswig-Holstein
  • Israel
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Ancona, Italy
        • Az. Ospedaliero-Universitaria - Ospedali Riuniti
      • Lecco, Italy
        • Ospedale Lecco
      • Milan, Italy
        • C. Besta Neurological Institute
      • Milan, Italy
        • Foundation Hospital Greater Policlinico
      • Rome, Italy
        • Istituti Fisioterapici Ospitalieri - Istituto Nazionale dei Tumori Regina Elena
  • Korea, Republic of
      • Asan, Korea, Republic of
        • Asan Medical Center
      • Daegu, Korea, Republic of
        • Yeungnam University Hospital
      • Daejeon, Korea, Republic of
        • Chungnam National University Hospital (CNUH)
      • Seoul, Korea, Republic of
        • Samsung Medical Center (SMC)
      • Seoul, Korea, Republic of
        • Seoul National University Bundang Hospital (SNUBH)
      • Seoul, Korea, Republic of
        • Seoul National University Hospital (SNUH)
      • Seoul, Korea, Republic of
        • The Catholic University of Korea, Seoul St. Mary's Hospital (CMC Seoul)
      • Seoul, Korea, Republic of
        • Yonsei University Severance Hospital (YUHS)
      • Suwon, Korea, Republic of
        • Ajou University Hospital (AUH)
  • Spain
      • Badalona, Spain
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital Clinic i Provincial de Barcelona
      • Barcelona, Spain
        • Hospital Universitari de Bellvitge-ICO Duran i Reynals
      • Madrid, Spain
        • Hospital Clinico San Carlos
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Fundacion Jimenes Diaz
      • Madrid, Spain
        • Hospital 12 de Octubre, Servicio de Oncologia Medica
      • Pamplona, Spain
        • Clinica Universidad de Navarra
  • Sweden
      • Stockholm, Sweden
        • Karolinska Institute
  • Switzerland
      • Lausanne, Switzerland
        • Centre Hospitalier Universitaire Vaudois (CHUV)
      • Zurich, Switzerland
        • Universitätsspital Zürich
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3410
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurology Clinics
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope
      • La Jolla, California, United States, 92093
        • University of California San Diego Moores Cancer Center (UCSD)
      • Los Angeles, California, United States, 90033
        • University of Southern California (USC)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
    • Florida
      • Orlando, Florida, United States, 32806
        • UF Health Cancer Center at Orlando Health
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University, Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago (UIC)
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0093
        • University of Kentucky, Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Burlington, Massachusetts, United States, 01805
        • Lahey Clinic Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine, Division of Oncology
    • New Jersey
      • Edison, New Jersey, United States, 08818
        • New Jersey Neuroscience Center - JFK Medical Center
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center, Department of Neurosurgery
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Arthur G. James Cancer Hospital and Solove Research Institute
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Health System
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Pennsylvania Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center (UPMC)
    • Texas
      • Dallas, Texas, United States, 75235-8808
        • UT Southwestern Medical Center
      • Dallas, Texas, United States, 75246
        • Baylor
      • Houston, Texas, United States, 77030
        • Methodist Hospital
      • Houston, Texas, United States, 77030
        • Methodist Neurological Institute
      • Houston, Texas, United States, 77030
        • The University of Texas Health Science Center at Houston (UTHSC)
      • Temple, Texas, United States, 76508
        • Scott and White Healthcare
      • The Woodlands, Texas, United States, 77380
        • Memorial Hermann The Woodlands
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Neuroscience Institute
      • Seattle, Washington, United States, 98195
        • University of Washington/Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Pathological evidence of GBM using WHO classification criteria.
  2. > 18 years of age.

  3. Received maximal debulking surgery and radiotherapy concomitant with Temozolomide (45-70Gy):

    1. Patients may enroll in the study if received Gliadel wafers before entering the trial
    2. Any additional treatments received prior to enrollment will be considered an exclusion.
    3. Minimal dose for concomitant radiotherapy is 45 Gy
  4. Karnofsky scale ≥ 70
  5. Life expectancy at least 3 months
  6. Participants of childbearing age must use effective contraception.
  7. All patients must sign written informed consent.
  8. Treatment start date at least 4 weeks out from surgery.
  9. Treatment start date at least 4 weeks out but not more than 7 weeks from the later of last dose of concomitant Temozolomide or radiotherapy.

Exclusion Criteria:

  1. Progressive disease (according to MacDonald Criteria). If pseudoprogression is suspected, additional imaging studies must be performed to rule out true progression.
  2. Actively participating in another clinical treatment trial
  3. Pregnant

  4. Significant co-morbidities at baseline which would prevent maintenance Temozolomide treatment:

    1. Thrombocytopenia (platelet count < 100 x 103/μL)
    2. Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
    3. CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
    4. Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
    5. Total bilirubin > upper limit of normal
    6. Significant renal impairment (serum creatinine > 1.7 mg/dL)
  5. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
  6. Infra-tentorial tumor
  7. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
  8. History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to DTIC.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NovoTTF-100A device in combination with Temozolomide
patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.
Device: NovoTTF-100A device
patients will be treated continuously with the NovoTTF-100A device, in addition to Temozolomide. NovoTTF-100A treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.
Active Comparator: Temozolomide alone, as the best known standard of care
Patients will be treated with Temozolomide, as the best known standard of care for Glioblastoma Multiforme patients.
Drug: Temozolomide

maintenance Temozolomide will be administered according to the approved dosing scheme as follows: Maintenance Phase Cycle 1: Four weeks after completing the Temozolomide + Radiotherapy phase, Temozolomide is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment.

Cycles 2-6: At the start of Cycle 2, the dose is escalated to 200 mg/m2, if the CTC non-hematologic toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea and vomiting), absolute neutrophil count (ANC) is ≥ 1.5 x 109/L, and the platelet count is ≥ 100 x 109/L. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival (PFS) time
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NovoCure Ltd.

Investigators

  • Study Director: Roger Stupp, MD, University Hospital, Zürich
  • Study Director: Philip H. Gutin, MD, Memorial Sloan Kettering Cancer Center
  • Study Director: Eric T. Wong, MD, Beth Israel Deaconess Medical Center
  • Study Director: Herbert H. Engelhard, MD, PhD, University of Illinois at Chicago
  • Study Director: Manfred Westphal, Prof. MD, Universitätsklinikum Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

June 5, 2009

First Submitted That Met QC Criteria

June 8, 2009

First Posted (Estimate)

June 9, 2009

Study Record Updates

Last Update Posted (Actual)

April 10, 2017

Last Update Submitted That Met QC Criteria

April 7, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EF-14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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