Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM)
- Conditions
- Glioblastoma Multiforme
- Interventions
- Device: NovoTTF-100A device
- Registration Number
- NCT00916409
- Lead Sponsor
- NovoCure Ltd.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 700
-
Pathological evidence of GBM using WHO classification criteria.
-
> 18 years of age.
-
Received maximal debulking surgery and radiotherapy concomitant with Temozolomide (45-70Gy):
- Patients may enroll in the study if received Gliadel wafers before entering the trial
- Any additional treatments received prior to enrollment will be considered an exclusion.
- Minimal dose for concomitant radiotherapy is 45 Gy
-
Karnofsky scale ≥ 70
-
Life expectancy at least 3 months
-
Participants of childbearing age must use effective contraception.
-
All patients must sign written informed consent.
-
Treatment start date at least 4 weeks out from surgery.
-
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.
-
Progressive disease (according to MacDonald Criteria). If pseudoprogression is suspected, additional imaging studies must be performed to rule out true progression.
-
Actively participating in another clinical treatment trial
-
Pregnant
-
Significant co-morbidities at baseline which would prevent maintenance Temozolomide treatment:
- Thrombocytopenia (platelet count < 100 x 103/μL)
- Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
- CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)
- Significant liver function impairment - AST or ALT > 3 times the upper limit of normal
- Total bilirubin > upper limit of normal
- Significant renal impairment (serum creatinine > 1.7 mg/dL)
-
Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
-
Infra-tentorial tumor
-
Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
-
History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to DTIC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NovoTTF-100A device in combination with Temozolomide 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. Temozolomide alone, as the best known standard of care Temozolomide Patients will be treated with Temozolomide, as the best known standard of care for Glioblastoma Multiforme patients.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) time 5 years
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 5 years
Trial Locations
- Locations (89)
Lahey Clinic Medical Center
🇺🇸Burlington, Massachusetts, United States
Geisinger Health System
🇺🇸Danville, Pennsylvania, United States
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭Lausanne, Switzerland
University of Illinois at Chicago (UIC)
🇺🇸Chicago, Illinois, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Barrow Neurology Clinics
🇺🇸Phoenix, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
University of California San Diego Moores Cancer Center (UCSD)
🇺🇸La Jolla, California, United States
University of Southern California (USC)
🇺🇸Los Angeles, California, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Emory University, Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
New Jersey Neuroscience Center - JFK Medical Center
🇺🇸Edison, New Jersey, United States
The Ohio State University Arthur G. James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Yonsei University Severance Hospital (YUHS)
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Karolinska Institute
🇸🇪Stockholm, Sweden
Fundacion Jimenes Diaz
🇪🇸Madrid, Spain
UniversitätsSpital Zürich
🇨🇭Zurich, Switzerland
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Kentucky, Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Maine Medical Center
🇺🇸Scarborough, Maine, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Scott and White Healthcare
🇺🇸Temple, Texas, United States
Mount Sinai Medical Center, Department of Neurosurgery
🇺🇸New York, New York, United States
Methodist Neurological Institute
🇺🇸Houston, Texas, United States
University Hospital Graz
🇦🇹Graz, Austria
Medical University of Vienna
🇦🇹Vienna, Austria
SMZ-Süd/Kaiser-Franz-Josef-Spital
🇦🇹Vienna, Austria
Ajou University Hospital (AUH)
🇰🇷Suwon, Korea, Republic of
Chungnam National University Hospital (CNUH)
🇰🇷Daejeon, Korea, Republic of
Seoul National University Hospital (SNUH)
🇰🇷Seoul, Korea, Republic of
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Ospedale Lecco
🇮🇹Lecco, Italy
CHU Amiens Sud-Salouel
🇫🇷Amiens, France
Tom Baker Cancer Center
🇨🇦Calgary, Alberta, Canada
CHU Angers
🇫🇷Angers, France
Hospital del Mar
🇪🇸Barcelona, Spain
Juravinski Cancer Centre
🇨🇦Hamilton,, Ontario, Canada
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Hospital Universitari de Bellvitge-ICO Duran i Reynals
🇪🇸Barcelona, Spain
Notre-Dame Hospital (CHUM)
🇨🇦Montreal, Quebec, Canada
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Foundation Hospital Greater Policlinico
🇮🇹Milan, Italy
Hôpital Saint André Centre Hospitalier Universitaire (CHU) des Hôpitaux de Bordeaux
🇫🇷Bordeaux, France
(CHUS) Centre Hospitalier Universitaire de Sherbrooke, Service de Neurochirurgie
🇨🇦Sherbrooke, Quebec, Canada
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
Seoul National University Bundang Hospital (SNUBH)
🇰🇷Seoul, Korea, Republic of
Hospital of Neurology Pierre Wertheimer
🇫🇷Lyon, France
Group Hospitals Pitie-Salpetriere
🇫🇷Paris, France
Centre Hospitalo-Universitaire de Toulouse Purpan
🇫🇷Toulouse, France
Medical University Heidelberg
🇩🇪Heidelberg, Germany
Asan Medical Center
🇰🇷Asan, Korea, Republic of
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Montreal Neurological Institute
🇨🇦Montreal, Quebec, Canada
McGill - Gerald Bronfman Centre for Clinical Research in Oncology -
🇨🇦Montreal, Quebec, Canada
Na Homolce Hospital
🇨🇿Prague, Czech Republic
Istituti Fisioterapici Ospitalieri - Istituto Nazionale dei Tumori Regina Elena
🇮🇹Rome, Italy
Az. Ospedaliero-Universitaria - Ospedali Riuniti
🇮🇹Ancona, Italy
C. Besta Neurological Institute
🇮🇹Milan, Italy
University Hospital of Schleswig-Holstein
🇩🇪Kiel, Germany
Hospital 12 de Octubre, Servicio de Oncología Médica
🇪🇸Madrid, Spain
Samsung Medical Center (SMC)
🇰🇷Seoul, Korea, Republic of
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Baylor
🇺🇸Dallas, Texas, United States
Memorial Hermann The Woodlands
🇺🇸The Woodlands, Texas, United States
Washington University School of Medicine, Division of Oncology
🇺🇸St. Louis, Missouri, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
The Catholic University of Korea, Seoul St. Mary's Hospital (CMC Seoul)
🇰🇷Seoul, Korea, Republic of
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
University of Washington/Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
The University of Texas Health Science Center at Houston (UTHSC)
🇺🇸Houston, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States