EF-25 / METIS: A pivotal (analogous to drug Phase III), randomized, controlled study, designed to evaluate the efficacy and safety of Tumor Treating Fields (TTFields), generated by a medical device, NovoTTF-200M in patients with 1-10 newly diagnosed brain metastases from non-small cell lung cancer (NSCLC).
The METIS study is intended for patients who have recently been diagnosed with brain metastases from non-small cell lung cancer (NSCLC). This clinical study is evaluating the safety and efficacy of the NovoTTF-200M device for this indication, when added after the standard stereotactic radiosurgery (SRS) normally given to patients in this condition. The NovoTTF-200M device delivers Tumor Treating Fields (TTFields) [About TTFields] to the cancer in the brain.
Novocure, the study sponsor, maintains this website to help patients get basic information about the clinical study.
If you would like to take part in the METIS study, please contact one of the participating centers [METIS Centers] as soon as possible. If you have questions concerning your medical condition and recommended treatment, please consult with your treating doctor.
Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division [Science of TTFields]. TTFields may interfere with the electrically-charged cellular components of cancer cells, disrupting their normal function and may ultimately lead to cell death. As a result, the cancer cell division may be slowed, or even stopped, inhibiting tumor growth.
TTFields are delivered to the body region where the tumor is located using an investigational medical device called NovoTTF-200T. NovoTTF-200M is a portable, lightweight, battery-operated device designed to deliver TTFields.
Patients receiving TTFields need to wear four adhesive patches called INE Transducer Arrays (arrays) on their scalp, which deliver the TTFields non-invasively to the cancer site. The device is intended for continuous use by patients [Living with TTFields].
The use of NovoTTF-200M for the treatment of brain metastases from non-small cell lung cancer (NSCLC) is investigational; it has not been approved by the U.S. Food and Drug Administration (FDA) for this use. The safety and effectiveness of TTFields in this condition is still unknown, and will be evaluated in this clinical study [The METIS Trial].
TTFields therapy has been approved for adult patients with recurrent (as a monotherapy) and newly diagnosed glioblastoma multiforme (GBM) ) (in combination with a chemotherapy called temozolomide), in the United States under the Premarket Approval (PMA) pathway, has obtained a CE mark in Europe, and is approved in Japan for the same indication. The use of TTFields concurrent with chemotherapy has also been CE marked in Europe and approved for adult patients with malignant pleural mesothelioma (MPM) under FDA’s Humanitarian Device Exemption (HDE) pathway.
In May 2020, the China National Medical Products Administration (NMPA) approved Optune® for the treatment of newly diagnosed and recurrent glioblastoma. In August 2020, Optune Lua™ launched for the treatment of malignant pleural mesothelioma (MPM) in Hong Kong.
the METIS trial
The METIS study (also known as the “EF-25”) is a pivotal (analogous to a Phase 3 drug trial), randomized, controlled study, designed to evaluate the efficacy and safety of Tumor Treating Fields (TTFields) generated by a medical device, NovoTTF-200M [About TTFields] in patients with 1-10 newly diagnosed brain metastases from non-small cell lung cancer (NSCLC). TTFields are administered to patients concomitantly with the best standard of care treatments that would normally be used to treat this condition. The study is expected to enroll a total of 270 patients. The study is now enrolling patients in multiple centers around the world. [METIS Centers].
Please note: Depending on the country, some sites will use the NovoTTF-100 device while others will use the NovoTTF-200 series. Please see clinicaltrials.gov for specific study, device, and protocol information.
the METIS study design
Patients with 1 inoperable or 2-10 newly diagnosed brain metastases from NSCLC are candidates for this study. Final eligibility can only be determined by the clinical study physician in one of the clinical study sites. All patients enrolled in the study will receive stereotactic radiosurgery (SRS) for their brain metastasis in addition to the best standard of care treatments for their lung cancer and brain metastases, similar to patients who are not participating in the study. All patients will be randomly assigned to one of two groups:
- TTFields Group: TTFields administered using NovoTTF-200M, in addition to best standard of care
- Standard of Care Group (control): Best standard of care without TTFields.
Each patient will have 50% chance of entering each of the two groups as determined by a “randomization process” (similar to a coin flip). Patients enrolled in the Standard of Care Group might still be able to receive TTFields after their disease in the brain progresses twice according to the study protocol [Q&A]. Eligible patients can be enrolled in the study no later than 21 days after written informed consent.
If assigned to the TTFields Group, the patient will receive continuous TTFields treatment using NovoTTF-200M. In order to apply the device, the patient needs to wear four arrays on the scalp [About TTFields]. Array placement will require shaving of the entire scalp before starting to use the device, and twice a week as long as its use continues.
The use of the device will start in an outpatient setting and will include training on the operation of the equipment by a qualified Device Support Specialist (DSS). Patients will continue to use the device at home [Living with TTFields]. Patients using NovoTTF-200M can maintain the use of the device alone (with the help of a family member or a care giver if needed) or receive support from their DSS.
The device is 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 their normal daily routines.
Standard of Care Group
Patients assigned to the Standard of Care Group will receive standard dosing of approved medications, the treatments which are the most appropriate for any medical condition (including lung cancer), according to best practice of the treating study physician. Patients might benefit from receiving comprehensive follow up exams every 8 weeks that include some testing not typically included in standard of care at no cost to the patient. Patients enrolled in the Standard of Care Group might still be able to receive TTFields after their disease in the brain progresses twice according to the study protocol.
In addition, all study participants contribute to future patients by providing additional information and data used to assess the efficacy of TTFields.
Using the Device
To receive treatment, the patient needs to wear adhesive patches called arrays on their scalp which deliver the TTFields non-invasively to the tumor location. Array placement may require shaving of the contact site before starting to use the device, and twice a week for as long as its use continues. The arrays are replaced and re-applied on a regular basis for as long as the patient is receiving the treatment.
The use of NovoTTF-200M will include training on the operation of the equipment by a qualified Device Support Specialist (DSS). Patients will continue to use the device at home [Living with TTFields].
Once trained, patients using NovoTTF-200M can setup and use the device themselves (with the help of a family member or a caregiver 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 their normal daily routines.
For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with a METIS study physician:
Key Inclusion Criteria (summary, not complete list):
- Newly diagnosed with 1 inoperable brain metastases, or 2-10 previously untreated brain metastases from non-small cell lung cancer (NSCLC).
- All brain metastases are amenable to stereotactic radiosurgery (SRS).
- At least 18 years of age.
Key Exclusion Criteria (summary, not complete list)
- Prior treatment for brain metastasis.
- Being unable to operate the NovoTTF-200M device independently, or with the help of a caregiver.
- Current pregnancy.
- Significant illnesses not associated with the primary disease.
- Implanted electronic devices in the brain.
Expected total enrollment 270 patients in multiple centers around the world. Please contact the center closest to you as soon as possible if you would like to participate in the METIS study.
There will be no cost to participate in this study. The study sponsor (Novocure) will pay for reasonable treatment related supplies, including NovoTTF-200M and accessories. Patients and their insurance will be responsible for medical treatments received in the normal course of patient care.* The study sponsor will also reimburse patients for reasonable travel costs directly related to the study’s procedures. Such reimbursements are done according to the policy of the study center at which the patient is being treated. Prior to enrolling in the study, please consult with the clinical study team at the center about the local reimbursement policy and your rights.
*Some regional differences may apply. Please contact the study center closest to you for more information
An updated list of medical centers participating in METIS and their contact information can be accessed using the following link clinicaltrials.gov.
If you are unable to reach a study center and/or receive complete information about the study, please email patient info with questions and mention “METIS” in the subject line.
living with TTFields
Patients participating in the METIS study on TTFields treatment use the device continuously for an average of at least 18 hours a day, but may take breaks during daily use for some activities. The treating physician may modify the treatment schedule and use of the device as needed.
The DSS will provide device support to patients and caregivers.
Please note: While the DSS provides comprehensive technical support, direct all medical questions to your study clinician.
NovoTTF-200M is intended for continuous use for at least 18 hours a day. The device should not interfere with household or personal electrical devices. There is no exposure of TTFields to non-users, such as family members and co-workers.
What does it look like?
NovoTTF-200M is a wearable, portable device. Use of the device requires shaving of the contact site, and the application of adhesive patches called arrays to the scalp. Naturally, some patients may be concerned about their appearance or their lifestyle while using the device. The arrays and the wires connecting to the device can be concealed underneath the patient’s clothes. By doing so, the bag carrying the device may be the only element of NovoTTF-200M visible to others. The medical team will provide personalized assistance specific to each patient on how best to wear the device
In addition to regularly shaving the contact area, patients will regularly change their arrays to ensure continuous treatment. The medical team will assist in creating a plan and instructing patients on array placement.
The device is designed to allow patients to maintain their lifestyle without interference to their daily routines. Consult the treating physician ahead of time regarding any activity in question. In addition, the DSS can provide information to address lifestyle concerns.
The device bag can be worn as a shoulder bag, a backpack, a messenger bag, or hand-held. The total weight of the device including a battery is around 1.3 kilograms, or 2.7 pounds. The DSS can provide as many batteries as needed.
In order to ensure continuous treatment, patients will plug NovoTTF-200M in to an AC adapter when staying in a location for more than a few hours.
science of TTFields
Cancer cells divide and multiply rapidly within the brain metastases from non-small cell lung cancer (NSCLC) tumor. These cancer cells carry different types of electrically charged elements that play a role during the cell division process. Other healthy cells in the treatment area multiply at a much slower rate, if at all.
TTFields Mechanism of Action
NovoTTF-200M in this study delivers low intensity, wave-like electric fields to the location of the tumor. These fields are known as Tumor Treating Fields (TTFields).
Pre-clinical 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 may ultimately lead to cell death.
In addition, cancer cells also contain miniature building blocks that 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 also electrically charged. As a result, the cancer cell division is slowed, or even stopped, inhibiting tumor growth.
A summary of TTFields’ mechanism of action is illustrated in the following animation:
TTFIELDS ARE NOT APPROVED FOR THE TREATMENT OF BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC). THE SAFETY AND EFFICACY OF TTFIELDS FOR THIS INDICATION HAS NOT BEEN ESTABLISHED.
Past Clinical Experience
To date, the sponsor has investigated a number of similar devices developed to deliver TTFields to different tumors. The main difference between the previously studied devices and NovoTTF-200M is the frequency of TTFields provided by each device. The frequency is adjusted by the manufacturer in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.
NovoTTF-100L, a previous model of NovoTTF-200M, has been evaluated in a pilot study of 42 patients with inoperable non-small cell lung cancer patients who received TTFields in combination with standard chemotherapy to evaluate the safety of TTFields in this indication.
A similar device, NovoTTF-200A (also called Optune®), delivers TTFields to the brain and is approved by the FDA under the Premarket Approval (PMA) pathway for the treatment of adults with recurrent and newly diagnosed glioblastoma, a type of aggressive primary brain tumor. Optune has a CE Mark in Europe for the treatment of glioblastoma, and is also approved in Japan and Greater China. For the treatment of malignant pleural mesothelioma (MPM), Optune Lua™ has a CE Mark in Europe and was FDA approved under the Humanitarian Device Exemption (HDE) pathway for this use.
Based on the science behind TTFields and the clinical results to date, NovoTTF-200M is not expected to have systemic side effects in patients with brain metastases from non-small cell lung cancer (NSCLC). In previous studies performed with Optune, the device investigated in glioblastoma, a high percentage of patients have experienced local skin irritation beneath the arrays, which was mild to moderate in severity in the vast majority of cases.
In the aforementioned study for non-small cell lung cancer, there were no serious systemic side effects attributed by the study doctors to TTFields. The only side effect which was related to the device was mild to moderate skin irritation under the arrays placed on the skin.
The information provided in this website is partial, and you should consult with your treating physician concerning the complete safety profile of TTFields.
What is the objective of this study?
This study is designed to evaluate the safety and efficacy of TTFields treatment after stereotactic radiosurgery (SRS) for 1 – 10 brain metastases from non-small cell lung cancer (NSCLC).
How can I participate in the METIS study?
What are the expected side effects of TTFields?
The use of NovoTTF-200M is not expected to have systemic side effects, based on our clinical data to date. Some patients have experienced skin irritation beneath the arrays. For more information, see Science of TTFields.
When TTFields are delivered, the arrays may cause mild warming and tingling of the skin underneath them.
Please consult with a study physician at one of the centers participating in the study for additional information about potential side effects from using NovoTTF-200M and the other treatments in the METIS clinical study [METIS Centers].
Do I need to carry the device all the time?
Patients 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. The device and the portable battery weigh about 1.3 kilograms, or 2.7 pounds, altogether and can be carried in a dedicated shoulder bag or backpack when walking around.
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 electrical devices. There is no exposure of TTFields to non-users, such as family members and co-workers.
How will the device affect my social life?
The arrays will be concealed 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.