Ignite Creation Date:
2024-05-06 @ 10:51 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03377491
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-04-10
First Post:
2017-12-06
Brief Title:
Effect of Tumor Treating Fields TTFields 150 kHz as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel PANOVA-3
Sponsor:
NovoCure Ltd
Organization:
NovoCure Ltd
Study Overview
Official Title:
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Brief Summary
The study is a prospective randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields TTFields in combination with gemcitabine and nab-paclitaxel for front line treatment of locally-advanced pancreatic adenocarcinomaThe 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
The study is a prospective randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields TTFields in combination with gemcitabine and nab-paclitaxel for front line treatment of locally-advanced pancreatic adenocarcinomaThe 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 pancreatic adenocarcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with other chemotherapies including gemcitabine In addition TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment
In a pilot study 40 patients with locally advanced or metastatic pancreatic adenocarcinoma received gemcitabine together with TTFields 150 kHz or gemcitabine and nab-paclitaxel together with TTFields 150 kHz applied to the abdomen until disease progression The combination was well tolerated and the only device-related adverse event was contact dermatitis
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 2017
DESCRIPTION OF THE TRIAL
All patients included in this trial are patients with locally advanced pancreatic adenocarcinoma In addition all patients must meet all eligibility criteria
Eligible patients will be randomly assigned to one of two groups
1 Patients receive gemcitabine and nab-paclitaxel in combination with TTFields using the NovoTTF-200T System
2 Patients receive gemcitabine and nab-paclitaxel without TTFields
Patients will be randomized at a 11 ratio Baseline tests will be performed in patients enrolled in both arms If assigned to the NovoTTF-200T group the patients will be treated continuously with the device until progression in the abdomen On both arms patients who have progression outside the abdomen will switch to a second line treatment according to local practice
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 pancreatic adenocarcinoma with very few side effects
The effect of the electric fields TTFields TTF has demonstrated significant activity in in vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with other chemotherapies including gemcitabine In addition TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment
In a pilot study 40 patients with locally advanced or metastatic pancreatic adenocarcinoma received gemcitabine together with TTFields 150 kHz or gemcitabine and nab-paclitaxel together with TTFields 150 kHz applied to the abdomen until disease progression The combination was well tolerated and the only device-related adverse event was contact dermatitis
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 2017
DESCRIPTION OF THE TRIAL
All patients included in this trial are patients with locally advanced pancreatic adenocarcinoma In addition all patients must meet all eligibility criteria
Eligible patients will be randomly assigned to one of two groups
1 Patients receive gemcitabine and nab-paclitaxel in combination with TTFields using the NovoTTF-200T System
2 Patients receive gemcitabine and nab-paclitaxel without TTFields
Patients will be randomized at a 11 ratio Baseline tests will be performed in patients enrolled in both arms If assigned to the NovoTTF-200T group the patients will be treated continuously with the device until progression in the abdomen On both arms patients who have progression outside the abdomen will switch to a second line treatment according to local practice
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 pancreatic adenocarcinoma with very few side effects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
True
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None