TRIDENT – Glioblastoma Clinical Trial

overview

The TRIDENT study is for patients recently diagnosed with glioblastoma (GBM). This clinical trial is evaluating the safety and efficacy of Tumor Treating Fields (TTFields) delivered by the Optune® treatment paired with radiation therapy and temozolomide in newly diagnosed GBM patients [About TTFields]. 

All patients participating in this study will receive Optune® treatment [The TRIDENT Trial].

Novocure maintains this website to help patients get basic information about the study.

If you want to take part in the TRIDENT trial, please contact one of the participating centers [TRIDENT Centers] as soon as possible.  Consult your treating physician if you have questions about your medical condition and if a clinical trial is right for you.

about TTFields

What are TTFields?

Tumor Treating Fields (TTFields) are low-intensity wave-like electric fields, tuned to interfere with the division process of cancer cells [Science of TTFields]. 

TTFields are delivered to the region of the tumor using the Optune® medical device. The Optune® System is a portable, light-weight, battery operated device designed to deliver TTFields to glioblastoma (GBM) tumors.

Patients receiving TTFields need to wear four adhesive patches called “transducer arrays” on their scalp, which deliver the fields non-invasively to the location of the GBM tumor. The system is intended for continuous use by patients [Living with TTFields].

TTFields have been approved by the FDA for treatment of adult patients with recurrent and newly diagnosed GBM. What makes the TRIDENT study different is that is testing the use of Optune® together with radiation therapy (RT) and temozolomide (TMZ) in newly diagnosed patients.[The TRIDENT TRIAL].

the TRIDENT trial

The TRIDENT trial (also known as the “EF-32 trial”) is a randomized, controlled study, testing the safety and efficacy of Tumor Treating Fields (TTFields) from the Optune® System [About TTFields] together with radiation therapy and temozolomide in newly diagnosed glioblastoma (GBM) patients.

Patients in the study will use Optune® as well as the other standard of care treatments for GBM.  The trial is expected to enroll 950 patients. Enrollment is open in multiple centers in the US, Canada, Japan, and across Europe [TRIDENT Centers].

The TRIDENT Trial Design

This trial is for newly diagnosed GBM patients who, after surgery or biopsy, are good candidates for radiation therapy (RT) and temozolomide (TMZ) treatments.

Final eligibility can only be determined by a clinical trial physician in one of the clinical trial sites.

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

• The Experimental Group: TTFields using the Optune® system upfront with RT and TMZ followed by the use of Optune® and TMZ
• The Control Group: Beginning treatment of RT and TMZ, followed by the use of Optune® and TMZ

Each patient will have equal chance of entering each of the two groups as determined by a “randomization process.” [FAQ]. 

Patients will continue on TTFields for 24 months, a notable disease progression, or clinically unable to continue treatment. 

Experimental Group

Patients assigned to the the Experimental Group will receive continuous TTFields treatment using Optune® from the beginning of study treatment with RT and TMZfor 6 week.  Then the patient will continue treatment with Optune® and TMZ for six courses, and Optune will continue until second progression.

Control Group (Control Group)                       

Patients assigned to the Control Group (Control) will receive standard dosing of approved therapies, RT and TMZ, according to best practice of the treating trial physician.  After 6 weeks of RT and TMZ, the patient will then begin treatment with Optune® and TMZ for six courses, and continue Optune until second progression.

By participating in the study, all participants are assisting researchers in providing additional information and data used to assess the efficacy of TTFields, with the goal to assist future patients with this disease.

Using the Optune® System

To receive treatment, the patient needs to wear four adhesive patches called “transducer arrays,” applied directly to their scalp [About TTFields]. Transducer array placement requires the shaving of the entire scalp before starting to use the device, and twice a week as long as the patient continues to use Optune®.

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]. 

Once trained, patients using Optune® can setup and use the device themselves (with the help of a family member or a caregiver if needed) or receive support from Novocure.

Eligibility             

Inclusion Criteria*

1. Histologically confirmed diagnosis of GBM according to WHO classification criteria.
2. Age ≥ 22 years in US and Age ≥ 18 years in Ex-US
3. Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
4. Planned treatment with RT/TMZ followed by TTFields and maintenance TMZ (150-200 mg/m2 daily x 5 d, q28 days)
5. Karnofsky performance status ≥ 70
6. Life expectancy ≥ least 3 months

Exclusion Criteria* 

1. Progressive disease (per investigator’s assessment)
2. Infratentorial or leptomeningeal disease
3. Participation in another clinical treatment study during the pre-treatment and/or the treatment phase of the study
4. Pregnancy or breast-feeding.
5. Significant co-morbidities at baseline, which would preclude maintenance RT or TMZ treatment, as determined by the investigator.
6. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.

*For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with a TRIDENT trial physician [TRIDENT Centers] 

Enrollment

Expected total enrollment is 950 patients. The trial is active in multiple European and North American medical centers.  Please contact one of the participating centers if you would like to participate in the TRIDENT trial [TRIDENT CENTERS].

living with TTFields

Patients participating in the TRIDENT trial wear the system continuously for an average of at least 18 hours a day, but may take breaks during daily use for some activities. The treating physician might modify the treatment schedule and use of the device as needed.

Novocure will provide device support to patients and caregivers. 

Please note: While Novocure provides comprehensive technical support Optune®, direct all medical questions to your trial clinician.

Using the Optune® System

The Optune® system is intended for continuous use for at least 18 hours a day. Optune® does not interfere with household or personal electrical devices. There is no exposure of TTFields to non-users, such as co-workers and family members.

What does it look like?

Optune is a wearable, portable device. Use of Optune® requires shaving of the scalp and the application of four adhesive patches called “transducer arrays” to the head. Naturally, some patients may be concerned about their appearance or their lifestyle while using the system. Patients can cover Optune by wearing head coverings, with a loose-weave wig, headscarf, or loose-fitting hat that allows airflow. The medical team will provide personalized assistance specific to each patient for wearing the device comfortably.

In addition to regularly shaving their head, patients will regularly change their arrays to ensure continuous treatment. Your medical team will assist in creating a plan and instructing you on array placement.

In addition to head coverings, the wires connecting the transducer arrays to the device can be concealed underneath the patient’s clothes. By doing so, the bag carrying the system may be the only element of the Optune® system invisible to others.

Portability

The device is designed to allow patients to maintain their lifestyle without interference to their daily routines such as walking outdoors, shopping, and meeting friends and family. Consult the treating physician ahead of time regarding any activity in question. In addition, Novocure can provide information to address lifestyle concerns.

The system’s bag can be worn as a backpack, a shoulder or a side (cross-body) bag. The total weight of the system, including a battery, is around 1.3 kilograms, or 2.7 pounds. Novocure can provide as many portable batteries as needed for patients who maintain an active lifestyle, which includes outdoor activities.

In order to ensure continuous treatment, patients will plug the Optune system 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. 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.

TTFields Mechanism of Action

The Optune® device in this trial delivers low intensity, wave-like electric fields to the location of a glioblastoma tumor. These fields are known as Tumor Treating Fields (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 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 reversed, inhibiting tumor growth.

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

Past Clinical Experience

A number of systems developed to deliver TTFields to different tumors have been tested to date. The frequency is adjusted by the manufacturer of the systems in order to optimize the treatment for specific tumor types, based on data from laboratory experiments.

The Optune® system is approved by the FDA for the treatment of recurrent and newly diagnosed glioblastoma (GBM), a type of aggressive primary brain cancer.

Side effects

Based on the science behind TTFields and the clinical results to date, Optune® is not expected to have systemic side effects in patients with newly diagnosed 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.

The following is the list of Optune®-related adverse events:

• Skin irritation 
• Headache 
• Malaise 
• Muscle twitching 
• Fall 

There were no serious side effects assessed as related by the study doctors to TTFields. The most common side effect, which was related to the device, was mild to moderate skin irritation under the transducer arrays that were easily manageable, and reversible.

For more detailed information, please consult with your treating physician concerning the complete safety profile of TTFields.

FAQ

What is the objective of the study?  

This study is designed to test the safety and efficacy of beginning TTFields Treatment together with RT and TMZ therapy for newly diagnosed GBM patients. [The Trident Trial].

How can I take part in the TRIDENT trial?

Please contact an investigator at the trial center closest to you [TRIDENT Centers]. You may also contact Novocure, the trial sponsor, if you need assistance reaching a trial center.

Does the randomization process mean I may not receive treatment?

No. All patients will receive the standard of care. This means both arms will receive the Optune® system. Please see our Trial information for more detail. See the TRIDENT Trial for more information

Do I need to carry the device all the time?

The system 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. Patients may not necessarily be physically carrying the system 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 system 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 will 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 patients to continue with daily routines. You can wear head covers, such as a loose weave wig, headscarf, or a loose-fitting hat that allows for airflow to conceal the transducer arrays, and you may place the array wires underneath your clothes. Novocure will offer help and support related to appearance issues if you are using TTFields. For additional information, please see Living with TTFields.