EF-33 – Recurrent Glioblastoma Clinical Trial

overview

EF-33

The EF-33 trial is intended for patients who have recently been diagnosed with recurrent Glioblastoma Multiforme (GBM).

Optune® has been approved for the treatment of recurrent and newly diagnosed GBM by the Food and Drug Administration (FDA) in the United States under the Premarket Authorization (PMA) pathway and has obtained a CE mark in Europe for the same indications.  In addition TTFields have been recently approved as Optune Lua™ (formerly NovoTTF-100L) for malignant pleural mesothelioma by the FDA, in combination with chemotherapy, under the Humanitarian Device Exemption pathway.

This clinical trial is evaluating the effectiveness and safety of Optune® with a new design of transducer arrays, the High Intensity Transducer Arrays, as monotherapy in recurrent GBM, compared to using the standard transducer arrays.

The device will deliver Tumor Treating Fields (TTFields) to the brain, where the tumor is located.

Novocure, the trial sponsor, maintains this website to help patients get basic information about the clinical trial and facilitate their accessibility to the medical center that offers participation in the trial. If you would like to take part in the EF-33 trial, please contact the participating center as soon as possible. If you have questions concerning your medical condition and recommended treatment, please consult with your treating doctor.

about TTFields

Tumor Treating Fields (TTFields) is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. [Science of TTFields]. TTFields are delivered to the body region where the tumor is located using an investigational medical device, called Optune® with High Intensity Transducer Arrays. The device is a portable, light-weight, battery operated device designed to deliver TTFields to the brain.

Patients receiving TTFields need to wear four arrays on their scalp, which deliver the fields non-invasively to the brain and are replaced on a regular basis. [Living with TTFields]. The device is intended for continuous home use by patients.

Optune® has been approved for the treatment of recurrent and newly diagnosed GBM by the Food and Drug Administration (FDA) in the United States under the Premarket Authorization (PMA) pathway and has obtained a CE mark in Europe for the same indications.  In addition TTFields have been recently approved as Optune Lua (formerly NovoTTF-100L) for malignant pleural mesothelioma by the FDA, in combination with chemotherapy, under the Humanitarian Device Exemption pathway.

the EF-33 trial

The EF-33 trial is a prospective, pilot (analogous to a drug Phase II), single arm, historical control study designed to test effectiveness and safety of Tumor Treating Fields (TTFields) delivered through High Intensity Arrays in recurrent GBM. During the study, TTFields at 200 kHz are generated by a medical device, Optune® with High Intensity Transducer Arrays [About TTFields], which is used by the patient at home. The trial is expected to enroll a total of 25 patients.

The trial is now enrolling patients in Czech Republic. This is a monocentric trial, meaning that only one site is involved in the trial [EF-33 Center].

The EF-33 Trial Design

Patients who were recently diagnosed with recurrent GBM (first or second recurrence) are candidates for this trial. Final eligibility in the trial can only be determined by the clinical trial doctor at the clinical trial center.

Study Treatment

The patient will receive continuous TTFields (200 kHz) treatment using Optune® with High Intensity Transducer Arrays.  In order to apply the device, the patient needs to wear four arrays on their scalp, which deliver the fields non-invasively to the brain.

Transducer Array placement requires shaving of the scalp before starting to use the device. New sets of arrays will need to be applied on a regular basis for as long as the device is used.

The use of the device will start in an outpatient setting and will include training on the operation of the equipment by a qualified Novocure Device Support Specialist (DSS). Patients will continue to use the device at home [Living with TTFields]. Patients using Optune® with High Intensity Transducer Arrays can maintain the use of the device alone (with the help of a family member or a care giver if needed) or may receive support from their DSS.

The device is designed to be user-friendly and all technical aspects related to using it are maintained by the DSS. The DSS can also help patients in finding technical solutions, to allow each individual to receive TTFields while maintaining his/her normal daily routines.

Eligibility

For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with the EF-33 clinical study doctor.

Inclusion Criteria (summary, not complete list):

1. Diagnosis of GBM, with first or second radiological progression
2. At least 18 years of age
3. Agreement to participate in the clinical trial (“informed consent”)

Exclusion Criteria (summary, not complete list):

1. Infratentorial or leptomeningeal disease
2. Other serious medical conditions, which will not allow the participation in the study
3. Treatment with Optune® (for newly diagnosed or recurrent disease) prior to enrollment
4. Implanted pacemaker, defibrillator and implanted electronic devices in the brain

Enrollment

Expected total enrollment is 25 patients. The trial is now enrolling patients in Czech Republic. This is a monocentric trial, meaning that only one site is involved in the trial.

Please contact the center as soon as possible if you would like to participate in the EF-33 trial [EF-33 Center].

Trial Costs

The trial sponsor (Novocure) will pay for reasonable technical treatment-related supplies, including Optune® with High Intensity Transducer Arrays and accessories. Patients and their insurance will be responsible for medical treatments received in the normal course of patient care. The trial sponsor will also reimburse patients for some travel costs related to the trial’s procedures. Such reimbursement can be done only according to the policy and approval of the trial center at which the patient is being treated. Please consult with the clinical trial team at the center prior to enrolling in the trial about the local reimbursement policy and your rights.

living with TTFields

Patients participating in the EF-33 trial wear the device continuously but can take breaks during their daily use of the device, with average time on TTFields throughout the entire treatment period at least at 18 hours per day. The clinical trial doctor might modify the treatment schedule and use of the device as needed.

Novocure provides patients with technical support through a local Device Support Specialist (DSS).  While the DSS provides comprehensive technical support, the patient’s medical team will continue to address any medical questions and to make all treatment decisions for the patient.

The use of the Optune® with High Intensity Transducer Arrays requires shaving of the scalp and continuous operation of a medical device.

Naturally, some patients may be concerned about their appearance or their lifestyle while using the device.

To address these concerns, the Optune® was carefully designed to allow patients to maintain their lifestyle without interference to their normal daily routine, such as walking outdoors, shopping, and meeting friends and family. The treating doctor can consult with Novocure ahead of time regarding any activity in question. In addition, the local DSS can provide information for lifestyle concerns.

Novocure can provide as many batteries as needed for patients who maintain an active lifestyle, which includes outdoor activities.

The transducer arrays are placed on the shaved scalp.  Patients may wear head coverings, such as a loose weave wig or loose-fitting hat that allows for airflow, to cover the transducer arrays. Many options are available and financial support for the desired solution may be provided by Novocure according to the trial center’s policy and pursuant to Novocure’s approval.  Patients should consult with their medical team for information about such financial support.

The wires coming out of the transducer arrays can be easily concealed underneath the patient’s clothes. By doing so, the bag carrying the device may be the only element of  Optune®  visible to others.

The carrying bag is provided by Novocure to each patient and can be used as a backpack, a shoulder or a side (cross-body) bag. The carrying bag blends well with mainstream bag trends.

While the total weight of the device including a battery is around 1.2 kilograms, the vast majority of patients will not be physically carrying the device most of the time, but will rather use it while it is continuously placed in one location (e.g., on a desk, a table or on the floor inside the carrying bag).

The use of the device should not interfere with household or personal electrical devices. There is no known exposure of TTFields to non-users, such as co-workers and family members.

science of TTFields

Cancer cells divide and multiply rapidly within the brain cancer. These cancer cells carry different types of electrically charged elements that play a role during the cell division process. Other healthy cells in the brain multiply at a much slower rate, if at all, and/or have other different properties such as a different size, compared to the cancer cells. Thus, normal cells rarely include the same electric properties as the dividing cancer cells and are not expected to be affected by TTFields.

TTFields Mechanism of Action

Optune® with High Intensity Transducer Arrays used in this trial delivers low intensity, alternating electric fields to the tumor site through the skin and other more superficial tissues. These fields are known as Tumor Treating Fields or TTFields. Preclinical studies showed that due to the shape and size of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death. 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 interfere with the normal orientation of these tiny motors since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, resulting in cellular death or cell division reversal. This may lead to inhibition of tumor growth after continuous exposure to TTFields. TTFields may affect the healthy brain cells much less than cancer cells since healthy brain cells multiply at a much slower rate, if at all.

A summary of TTFields’ mechanism of action is illustrated in the following animation:

Past Clinical Experience

Previous clinical studies have proved the efficacy and safety of TTFields in recurrent and newly diagnosed GBM. Following the positive results of these clinical studies, Optune® has been approved by the FDA under the Premarket Authorization (PMA) pathway for the treatment of recurrent and newly diagnosed GBM. The same device has a CE Mark in Europe for the treatment of glioblastoma.

In addition TTFields have been recently approved as Optune Lua (formerly NovoTTF-100L) for malignant pleural mesothelioma by the FDA, in combination with chemotherapy, under the Humanitarian Device Exemption pathway.

For more information about the approved indications for use, please consult with your treating doctor.

Side Effects

Based on the science behind TTFields and the clinical results to date, Optune® with High Intensity Transducer Arrays is not expected to have device side effects in patients suffering from GBM.

In previous studies performed with Optune®, a high percentage of patients have experienced local skin irritation beneath the transducer arrays, which was mild to moderate in severity in the vast majority of cases.

In a previous clinical trial for recurrent GBM, the following device related adverse events were reported:

• Medical device site reaction – 18 of 116 patients (16%)
• Headache – 4 of 116 patients (3%)
• Malaise – 2 of 116 patients (2%)
• Muscle twitching – 1 of 116 patients (1%)
• Fall – 1 of 116 patients (1%)
• Skin ulcer – 1 of 116 patients (1%)

In the aforementioned study there were no serious side effects related by the clinical trial doctors to TTFields. The only side effect which was related to the device was mild to moderate skin irritation under the transducer arrays placed on the skin.

The information provided in this website is partial, and you should consult with your treating doctor concerning the complete safety profile of TTFields.

FAQ

What stage is the EF-33 trial?

The EF-33 trial for participants with recurrent GBM is a pilot study. Because Optune® with High Intensity Transducer Arrays is a device and not a drug, it does not follow the traditional Phase I, Phase II, Phase III process that an investigational new drug would follow. This Pilot Trial is similar in structure and purpose to a drug Phase II trial.

How can I take part in the EF-33 trial?

The trial is now enrolling participants in Czech Republic. This is a monocentric trial, meaning that only one site is involved in the trial. Please contact the investigator at the trial center. You may also contact Novocure, the trial sponsor, if you need assistance reaching the trial center.

Do participants pay to participate in the EF-33 trial?

No. The trial sponsor will provide Optune® with High Intensity Transducer Arrays and all supporting accessories free of charge. See the EF-33 trial for more information.

What are the expected side effects of TTFields?

The use of Optune® with High Intensity Transducer Arrays is not expected to have systemic side effects, based on our clinical data to date for various conditions. Participants have experienced skin irritation beneath the transducer arrays. For more information, see Science of TTFields.

When TTFields are delivered, the transducer arrays may cause mild warming and tingling of the scalp.

Please consult with the clinical trial doctor at the center participating in the trial for additional information about potential side effects from using Optune® with High Intensity Transducer Arrays in the EF-33 clinical trial.

Do I need to carry the device all the time?

The device and the battery weigh about 1.2 kilograms and can be carried in a dedicated shoulder bag or backpack when walking around. Participants may not necessarily be physically carrying the device most of the time, but will rather use it while it is continuously placed in one location (e.g. on a desk, a table or on the floor inside the carrying bag). The device was designed to allow the performance of normal daily routines.

Will the use of TTFields pose any risk to family members or other people?

The use of the device should not interfere with household or standard personal electronic devices. There is no exposure of TTFields to non-users, such as co-workers and family members.

How will the device affect my social life?

The device was designed to allow participants to continue with daily routines. You can wear head covers, such as a loose weave wig or a loose-fitting hat that allows for airflow to conceal the transducer arrays, and you may place the array wires underneath your clothes. The Device Support Specialist (DSS) will offer help and support related to appearance issues if you are using TTFields. For additional information, please see [Living with TTFields].

If I enroll in the EF-33 trial, will I receive other anti-cancer therapies in addition to TTFields?

Participants on the study will receive TTFields and can also receive the best supportive care available at the discretion of their treating doctor.

Other concomitant anti-cancer therapies or procedures beyond TTFields are prohibited.

How long do I need to wear the device in the EF-33 trial?

Participants wear the device throughout the day and night, for at least 18 hours a day. Participants may remove the device for short breaks to accommodate personal needs. Treatment on the trial continues until your clinical trial doctor diagnoses progression of the GBM according to the protocol or 18 months (the earlier of the two). The treatment may be discontinued due to a serious medical condition, as assessed by the clinical trial doctor. In addition, you may decide to stop the TTFields at any point in time after starting the use of the device. For more information about the EF-33 trial, see the EF-33 Trial or contact the participating center.