ZL-8301-001 Gastric Study
The ZL-8301-001 Gastric study is intended for patients who have recently been diagnosed with unresectable gastroesophageal junction (GEJ) adenocarcinoma or gastric (GC) adenocarcinoma.
This clinical study is evaluating the safety and efficacy of Tumor Treating Fields (TTFields) delivered by the NovoTTF-200T device when added to chemotherapy, which is normally given to patients in this condition [About TTFields].
Novocure GmbH (the study sponsor) and ZaiLab (the trial local agent) maintain this website and WeChat advertisements to help patients get basic information about this study.
TTFIELDS ARE NOT APPROVED FOR THE TREATMENT OF GASTRIC ADENOCARCINOMA OR GASTROESOPHOGEAL JUNCTION ADENOCARCINOMA. THE SAFETY AND EFFICACY OF TTFIELDS FOR THIS INDICATION HAS NOT BEEN ESTABLISHED.
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 the NovoTTF-200T. NovoTTF-200T is a portable, lightweight, battery-operated device designed to deliver TTFields to the region of the gastroesophageal junction (GEJ) adenocarcinoma or gastric (GC) adenocarcinoma.
Patients receiving TTFields need to wear four adhesive patches called ILE Transducer Arrays (arrays) on their abdomen, back and flanks, which deliver the fields non-invasively to the tumor location. The device is intended for continuous use by patients [Living with TTFields].
The use of NovoTTF-200T for the treatment of gastric is investigational; it has not been approved for this use. The safety and effectiveness of TTFields in this condition is still unknown, and will be evaluated in this clinical study [ZL-8301-001 Gastric 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 ZL-8301-001 gastric trial
The ZL-8301-001 Gastric study is a prospective, pilot (analogous to a drug Phase II), single arm, open-label, multi-center study designed to test the overall response rate of Tumor Treating Fields (TTFields) in combination with chemotherapy as a first-line treatment for patients with unresectable gastroesophageal junction (GEJ) adenocarcinoma or gastric (GC) adenocarcinoma.
During the study, TTFields are generated by a medical device, NovoTTF-200T [About TTFields]. The study is expected to enroll a total of 28 patients including 6 HER2 positive subjects. This study is taking place in Hong Kong and mainland China [ZL-8301-001 Gastric Trial Centers].
The ZL-8301-001 Gastric Study Design
Candidates for the study are patients who were diagnosed with unresectable gastroesophageal junction (GEJ) adenocarcinoma or gastric (GC) adenocarcinoma.
Candidates for the study must be previously untreated with systemic treatment for recurrent or metastatic disease (including chemotherapy, targeted therapy, and Onco-Immunotherapy), and with resection of primary gastric focus.
Final eligibility in the study 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 GEJ or GC similar to standard of care therapy for patients who are not participating in the study.
Patients will receive continuous TTFields (150 kHz) treatment using the NovoTTF-200T device concomitant to the standard of care, Oxaliplatin (130 mg/m^2 intravenous infusion will be administered once every 3 weeks) and Capecitabine (1000 mg/m^2 taken by mouth, twice daily on day 1-14, 3 weeks per cycle) (XELOX chemotherapy regimen). For HER-2 positive patients, trastuzumab is allowed based on XELOX regimen. Trastuzumab will be intravenously infused on day 1 of each cycle, 21 days per cycle.
Using the Device
To receive treatment, the patient needs to wear adhesive patches called arrays on their abdomen, back and flanks 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.
For the complete list of eligibility criteria please go to [clinicaltrials.gov] or consult with a study physician:
Inclusion Criteria (summary, not complete list):
- Willing to and be able to sign an informed consent form
- Male or female aged ≥ 18 years
- Be able to receive the treatment in compliance with the study protocol in the discretion of the investigator
- ECOG Performance status score 0 or1
- Histologically confirmed unresectable, locally advanced or metastatic gastroesophageal junction (GEJ) or gastric (GC) adenocarcinoma. The subject must be previously untreated with systemic treatment for recurrent or metastatic disease (including chemotherapy, targeted therapy, and Onco-Immunotherapy), and with resection of primary gastric focus.
- Subjects must have at least one measurable lesion as per RECIST 1.1 criteria; and the tumor assessment baseline should be performed and established by the investigator within 28 days prior to study treatment.
- Life expectancy ≥ 3 months
- The allowed previous treatment: Palliative radiotherapy for bone metastasis is allowed if it has been completed within 2 weeks prior to the study treatment and all treatment-related toxicity should be recovered to Grade 1 before enrollment, according to CTCAE 5.0.
- Women of childbearing potential must have a negative serum pregnancy test result during screening. Post-menopausal women and surgically sterilized women are not required to undergo a pregnancy test. Females of childbearing potential/males and its partners who are sexually active must agree to adopt methods of contraception from signing the ICFs to within at least 6 months after the last dose of study drug. Besides, male subjects must be willing to refrain from sperm donation during this time.
- Able to operate the NovoTTF-200T device independently or with the help of a caregiver.
Exclusion Criteria (summary, not complete list):
- White blood cell count (WBC) < 2 × 10^9 / L
- Absolute neutrophil count (ANC) < 1.5 × 10^9 / L
- Platelet count < 100 × 10^9 / L
- Hemoglobin < 90 g/L
- Serum albumin < 30 g/L
- Serum creatinine > 1.5 × ULN, or creatinine clearance< 60 mL/min/1.73 m^2 calculated by Cockcroft-Gault
There will be no cost to participate in this study. The study sponsor will pay for reasonable treatment related supplies, including NovoTTF-200M and accessories, Oxaliplatin, Capecitabine and (for HER2 subjects) trastuzumab, and related fees. 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.
An updated list of medical centers participating in ZL-8301-001 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 “ZL-8301-001 Gastric” in the subject line.
living with TTFields
Patients participating in the ZL-8301-001 Gastric 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.
Using the NovoTTF-200T Device
NovoTTF-200T 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-200T is a wearable, portable device. Use of the device may requires shaving of the treatment site and the application of four adhesive patches called arrays to the abdomen, back and flanks. 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 the NovoTTF-200T device visible to others. The medical team will provide personalized assistance specific to each patient for wearing the device comfortably.
In addition to regularly shaving the treatment area, patients will regularly change their arrays to ensure continuous treatment. The patient’s medical team will assist in creating a plan and instructing the patient on array placement.
The device is designed to allow patients to maintain their lifestyle without interference to their daily routines. Consult the investigator 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 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. Zai Labs can provide as many 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 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 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 GASTRIC ADENOCARCINOMA. 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 in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.
NovoTTF-100L, 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 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-200T is not expected to have systemic side effects in patients with gastric adenocarcinoma. 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 on gastric adenocarcinoma and gastroesophageal junction carcinoma when used with chemotherapy.
How can I participate in the ZL-8301-001 Gastric study?
What are the possible side effects of TTFields?
The use of the NovoTTF-200T device 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 the 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 the NovoTTF-200T device and the other treatments in the ZL-8301-001 Gastric clinical study [ZL-8301-001 Gastric 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.