Ignite Creation Date:
2024-05-06 @ 8:49 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02831959
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-03-10
First Post:
2016-07-08
Brief Title:
Pivotal Open-label Randomized Study of Radiosurgery With or Without Tumor Treating Fields TTFields for 1-10 Brain Metastases From Non-small Cell Lung Cancer NSCLC
Sponsor:
NovoCure GmbH
Organization:
NovoCure Ltd
Study Overview
Official Title:
Pivotal Open-label Randomized Study of Radiosurgery With or Without Tumor Treating Fields TTFields for 1-10 Brain Metastases From Non-small Cell Lung Cancer NSCLC
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study is a prospective randomized controlled phase III trial to test the efficacy safety and neurocognitive outcomes of advanced NSCLC patients following stereotactic radiosurgery SRS for 1 inoperable brain metastasis or 2-10 brain metastases treated with NovoTTF-200M and supportive treatment compared to supportive treatment alone The device is an experimental portable battery operated device for chronic administration of alternating electric fields termed TTFields or TTF to the region of the malignant tumor by means of surface insulated electrode arrays
Detailed Description:
PAST PRE-CLINICAL AND CLINICAL EXPERIENCE
The effect of the electric fields TTFields TTF has demonstrated significant activity in in vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies TTFields have also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment
In a pilot study 42 patients with advanced NSCLC who had tumor progression after at least one line of prior chemotherapy received pemetrexed together with TTFields 150 kHz applied to the chest and upper abdomen until disease progression Pless M et al Lung Cancer 2011 Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone
In addition a phase III trial of Optune 200 kHz as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival associated with minimal toxicity good quality of life and activity within the brain 14 response rate Stupp R et al EJC 2012 Finally a phase III trial of Optune combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life Stupp R et al JAMA 2015
Applying TTFields at 150 kHz to the brain for the treatment of 1-5 brain metastasis from NSCLC using the NovoTTF-100M device has been demonstrated to be safe in a pilot study where patients were randomized after local therapy of their brain metastasis by neurosurgery andor stereotactic radiosurgery to receive either NovoTTF-100M treatment or supportive care alone Eighteen 18 patients have been enrolled in the study There have been no device-related serious adverse events SAE reported to date Brozova H et al Neuro Oncol 2016
DESCRIPTION OF THE TRIAL
All patients included in this trial are patients with 1-10 brain metastases from NSCLC which are amenable to stereotactic radiosurgery SRS In addition all patients must meet all eligibility criteria
Eligible patients will be randomly assigned to one of two groups
1 Patients undergo SRS followed by TTFields using the NovoTTF-200M System
2 Patients undergo SRS alone and receive supportive care Patients in both arms of the study may receive systemic therapy for their NSCLC at the discretion of their treating physician
Patients will be randomized at a 11 ratio Baseline tests will be performed in patients enrolled in both arms If assigned to the NovoTTF-200M group the patients will be treated continuously with the device until second intracranial progression
On both arms patients who recur anywhere in the brain will be offered one of the following salvage treatments according to local practice including but not limited to
Surgery
Repeat SRS
Whole brain radiotherapy WBRT Patients on the control arm will be offered to cross over to the NovoTTF-200M arm of the study and receive TTFields with or without salvage therapy for second intracranial progression if the investigator believes it is in the best interest of the patient and patient agrees
SCIENTIFIC BACKGROUND
Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field These forces cause movement and rotation of electrically charged biological building blocks much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet
Electric fields can also cause muscles to twitch and if strong enough may heat tissues TTFields are alternating electric fields of low intensity This means that they change their direction repetitively many times a second Since they change direction very rapidly 150 thousand times a second they do not cause muscles to twitch nor do they have any effects on other electrically activated tissues in the body brain nerves and heart Since the intensities of TTFields in the body are very low they do not cause heating
The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity now termed TTFields Tumor Treating Fields cause a significant slowing in the growth of cancer cells Due to the unique geometric shape 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 related to other cellular components since they are electrically-charged as well As a result of these two effects tumor cell division is slowed results in cellular death or reverses after continuous exposure to TTFields
Other cells in the body normal healthy tissues are affected much less than cancer cells since they multiply at a much slower rate if at all In addition TTFields can be directed to a certain part of the body leaving sensitive areas out of their reach Finally the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues In conclusion TTFields hold the promise of serving as a brand new treatment for brain metastases from NSCLC with very few side effects
The effect of the electric fields TTFields TTF has demonstrated significant activity in in vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies TTFields have also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment
In a pilot study 42 patients with advanced NSCLC who had tumor progression after at least one line of prior chemotherapy received pemetrexed together with TTFields 150 kHz applied to the chest and upper abdomen until disease progression Pless M et al Lung Cancer 2011 Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone
In addition a phase III trial of Optune 200 kHz as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival associated with minimal toxicity good quality of life and activity within the brain 14 response rate Stupp R et al EJC 2012 Finally a phase III trial of Optune combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life Stupp R et al JAMA 2015
Applying TTFields at 150 kHz to the brain for the treatment of 1-5 brain metastasis from NSCLC using the NovoTTF-100M device has been demonstrated to be safe in a pilot study where patients were randomized after local therapy of their brain metastasis by neurosurgery andor stereotactic radiosurgery to receive either NovoTTF-100M treatment or supportive care alone Eighteen 18 patients have been enrolled in the study There have been no device-related serious adverse events SAE reported to date Brozova H et al Neuro Oncol 2016
DESCRIPTION OF THE TRIAL
All patients included in this trial are patients with 1-10 brain metastases from NSCLC which are amenable to stereotactic radiosurgery SRS In addition all patients must meet all eligibility criteria
Eligible patients will be randomly assigned to one of two groups
1 Patients undergo SRS followed by TTFields using the NovoTTF-200M System
2 Patients undergo SRS alone and receive supportive care Patients in both arms of the study may receive systemic therapy for their NSCLC at the discretion of their treating physician
Patients will be randomized at a 11 ratio Baseline tests will be performed in patients enrolled in both arms If assigned to the NovoTTF-200M group the patients will be treated continuously with the device until second intracranial progression
On both arms patients who recur anywhere in the brain will be offered one of the following salvage treatments according to local practice including but not limited to
Surgery
Repeat SRS
Whole brain radiotherapy WBRT Patients on the control arm will be offered to cross over to the NovoTTF-200M arm of the study and receive TTFields with or without salvage therapy for second intracranial progression if the investigator believes it is in the best interest of the patient and patient agrees
SCIENTIFIC BACKGROUND
Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field These forces cause movement and rotation of electrically charged biological building blocks much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet
Electric fields can also cause muscles to twitch and if strong enough may heat tissues TTFields are alternating electric fields of low intensity This means that they change their direction repetitively many times a second Since they change direction very rapidly 150 thousand times a second they do not cause muscles to twitch nor do they have any effects on other electrically activated tissues in the body brain nerves and heart Since the intensities of TTFields in the body are very low they do not cause heating
The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity now termed TTFields Tumor Treating Fields cause a significant slowing in the growth of cancer cells Due to the unique geometric shape 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 related to other cellular components since they are electrically-charged as well As a result of these two effects tumor cell division is slowed results in cellular death or reverses after continuous exposure to TTFields
Other cells in the body normal healthy tissues are affected much less than cancer cells since they multiply at a much slower rate if at all In addition TTFields can be directed to a certain part of the body leaving sensitive areas out of their reach Finally the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues In conclusion TTFields hold the promise of serving as a brand new treatment for brain metastases from NSCLC with very few side effects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None