• Progression Free Survival (PFS) time [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  

• Overall survival (OS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• Progression free survival at 6 months (PFS6) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• 1% and 2-year survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• Radiological response (Macdonald criteria) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• Quality of life assessment (EORTC QLQ-C30) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• Adverse events severity and frequency [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  

PAST CLINICAL EXPERIENCE:

The effect of the electric fields generated by the NovoTTF-100A device (TTFields) has been tested in a small scale pilot trial in 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 trials is 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. The recruitment of 236 patients to another ongoing clinical trial (designated EF-11) designed to test the efficacy and safety of the NovoTTF-100A in recurrent GBM, has recently completed.

DESCRIPTION OF THE TRIAL:

Newly diagnosed GBM patients who:

• Underwent a biopsy or surgery followed by radiation therapy in combination with Temozolomide chemotherapy, AND

• Meet all of the requirements for participation in the study 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 who meet inclusion/exclusion criteria 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). If assigned to the NovoTTF-100A in combination with Temozolomide group, the patients will be treated continuously with the device, as long as under the treatment with Temozolomide and a second line of treatment the disease remains stable or regressing. Such second line could 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 electrodes on the head. Electrode placement will require shaving of the scalp before 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 under the treatment with a second line of 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 and ECG will be performed. A routine MRI of the head will be performed at baseline and every second month thereafter. 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.