PANOVA-3 – Pancreatic Cancer Clinical Trial
The PANOVA-3 study is a pivotal, randomized, open-label study of Tumor Treating Fields (TTFields, 150kHz) concomitant with gemcitabine and nab-paclitaxel for front-line treatment of locally-advanced pancreatic adenocarcinoma.
The PANOVA-3 study is intended for patients who have recently been diagnosed with locally advanced, pancreatic adenocarcinoma that cannot be treated with surgery. Pancreatic adenocarcinoma is the most common type of pancreatic cancer. This clinical study is evaluating the safety and efficacy of the NovoTTF-200T device for use in pancreatic adenocarcinoma, when added to gemcitabine and nab-paclitaxel, which are normally given to patients in this condition. The NovoTTF-200T is a non-invasive medical device that delivers Tumor Treating Fields (TTFields) [About TTFields] to the cancer in the abdominal region, where the tumor is located.
Novocure GmbH, the study sponsor, maintains this website to help patients get basic information about the study.
If you want to take part in the PANOVA-3 study, please contact one of the participating centers [PANOVA-3 Centers] as soon as possible.
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 ultimately may 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-200T is a portable, lightweight, battery-operated device designed to deliver TTFields of 150kHz.
Patients receiving TTFields need to wear four adhesive patches called ILE Transducer Arrays (arrays) on their abdomen, which deliver the TTFields non-invasively to the cancer site. The device is intended for continuous home use by patients [Living with TTFields].
NovoTTF-200T for the treatment of pancreatic cancer is investigational; it has not been approved by the U.S. Food and Drug Administration (FDA). The safety and effectiveness of TTFields in this condition is still unknown, and will be evaluated in this clinical study.
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.
the PANOVA-3 trial
The PANOVA-3 study is pivotal, randomized, open-label study of Tumor Treating Fields (TTFields, 150kHz), generated by the medical device NovoTTF-200T [About TTFields]. Study patients use the device concomitant with weekly gemcitabine and nab-paclitaxel for treatment of pancreatic cancer. The study is expected to enroll 556 patients in centers around the world [PANOVA-3 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 PANOVA-3 Study Design
The study is intended for patients diagnosed with locally-advanced, pancreatic adenocarcinoma that cannot be treated with surgery. Final eligibility can only be determined by the clinical study physician in one of the clinical study centers.
All patients enrolled in the study will receive a standard of care treatment for their pancreatic cancer with gemcitabine and nab-paclitaxel, similar to patients who are not participating in the study. All patients will be randomly assigned to one of two groups:
- The TTFields Group: TTFields using the NovoTTF-200T device in addition to standard of care gemcitabine and nab-paclitaxel.
- The Standard of Care Group (control): standard of care gemcitabine and nab-paclitaxel.
Each patient will have 50% chance of entering each of the two groups as determined by a “randomization process” (similar to a coin flip). Eligible patients can be enrolled in the study no later than 28 days after written informed consent.
If assigned to the TTFields Group, the patient will receive continuous TTFields treatment using the NovoTTF-200T device.
Using the Device
To receive treatment, the patient needs to wear adhesive patches called arrays on their abdomen 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-200T 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-200T 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.
In addition, patients will receive standard of care gemcitabine and nab-paclitaxel.
Standard of Care Group
Patients assigned to the Standard of Care Group will receive standard of care gemcitabine and nab-paclitaxel. Patients might benefit from receiving comprehensive follow up exams every 4 weeks that include some testing not typically included in standard of care at no cost to the patient.
In addition, all study participants contribute to future patients by providing additional information and data used to assess the efficacy of TTFields.
For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with a PANOVA-3 study physician:
Key Inclusion Criteria (summary, not complete list):
- 18 years of age and older.
- Histologically confirmed diagnosis of pancreatic cancer.
- Life expectancy of ≥ 12 weeks.
- Diagnosis of locally advanced, pancreatic adenocarcinoma that cannot be treated with a surgery.
- Amenable to receive weekly gemcitabine and nab-paclitaxel and able to operate NovoTTF-200T.
- Signed informed consent form for the study protocol.
Key Exclusion Criteria (summary, not complete list):
- Prior palliative treatment (e.g. surgery, radiation) to the tumor.
- Being unable to operate the NovoTTF-200T device independently or with the help of a caregiver.
- Women who are pregnant or breast feeding.
- Significant illnesses not associated with the primary disease.
- Implanted electronic devices (e.g. pacemaker) in the torso.
There will be no cost to participate in this study. The study sponsor (Novocure) will pay for reasonable treatment related supplies, including NovoTTF-200T and accessories. Patients and their insurance will be responsible for medical treatments received in the normal course of patient care. The study sponsor may 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.
living with TTFields
Patients participating in the PANOVA-3 study in the TTFields treatment group 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-200T is intended for continuous use for at least 18 hours a day. The device 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?
NovoTTF-200T 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 abdomen. 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-200T 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 gives patients the option to maintain their lifestyle without interference to their normal daily routine. Patients can consult the treating physician ahead of time regarding any activity in question. In addition, the DSS can provide information to address any 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. Novocure can provide as many portable batteries as needed.
In order to ensure continuous treatment, patients will plug NovoTTF-200T 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 pancreatic cancer 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-200T 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 PANCREATIC CANCER. 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-200T is the frequency of TTFields provided by each device. The frequency is adjusted by the manufacturer of the device in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.
NovoTTF-100L(P), a previous model of NovoTTF-200T, 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 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 now approved in Japan.
Based on the science behind TTFields and the clinical results to date, NovoTTF-200T is not expected to have systemic side effects in patients with pancreatic cancer. 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 pilot study is designed to evaluate the safety and efficacy of TTFields treatment together with gemcitabine and nab-paclitaxel, for the treatment of pancreatic cancer.
How can I participate in the PANOVA-3 study?
What are the expected side effects of TTFields?
The use of NovoTTF-200T is not expected to have systemic side effects, based on our clinical data to date. Some patients have experienced skin irritation beneath the arrays. 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-200T and the other treatments in the PANOVA-3 clinical study [PANOVA-3 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?
There is no exposure of TTFields to non-users, such as co-workers and family members. The use of the device should not interfere with household or standard personal electrical devices.
How will the device affect my social life?
You can use the device while maintaining most of your daily routines. The arrays will be concealed underneath your clothes. The Device Support Specialist (DSS) will offer help and support related to appearance or device lifestyle issues if you are using TTFields. For additional information, please see Living with TTFields.