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).
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ClinicalTrials.gov Identifier: NCT02831959 |
Recruitment Status :
Active, not recruiting
First Posted : July 13, 2016
Last Update Posted : March 10, 2023
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Tracking Information | |||||||||||||
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First Submitted Date ICMJE | July 8, 2016 | ||||||||||||
First Posted Date ICMJE | July 13, 2016 | ||||||||||||
Last Update Posted Date | March 10, 2023 | ||||||||||||
Study Start Date ICMJE | July 2016 | ||||||||||||
Estimated Primary Completion Date | December 2024 (Final data collection date for primary outcome measure) | ||||||||||||
Current Primary Outcome Measures ICMJE |
Time to intracranial progression [ Time Frame: 3 years ] | ||||||||||||
Original Primary Outcome Measures ICMJE |
Time to first cerebral progression [ Time Frame: 3 years ] | ||||||||||||
Change History | |||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Descriptive Information | |||||||||||||
Brief Title ICMJE | 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). | ||||||||||||
Official Title ICMJE | 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). | ||||||||||||
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 and/or 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:
Patients will be randomized at a 1:1 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:
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. |
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Study Type ICMJE | Interventional | ||||||||||||
Study Phase ICMJE | Phase 3 | ||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Brain Metastases From Non-small Cell Lung Cancer (NSCLC) | ||||||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||||||||
Estimated Enrollment ICMJE |
270 | ||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||
Estimated Study Completion Date ICMJE | December 2024 | ||||||||||||
Estimated Primary Completion Date | December 2024 (Final data collection date for primary outcome measure) | ||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
5. 1 inoperable brain metastasis or 2- 10 brain lesions per screening MRI, confirmed by contrast enhanced MRI amenable to SRS according to the following criteria: a. largest tumor volume < 10 cc b. longest tumor diameter < 3 cm c. Cumulative volume of all tumors ≤ 15 cc 6. At least one measurable disease per study protocol 7. Patients must be receiving optimal therapy for their extracranial disease according to local practice at each center. Patients may continue on systemic therapy while receiving TTFields. 8. Able to operate the NovoTTF-200M device independently or with the help of a caregiver 9. Clinical trials prior to enrollment are allowed, as long as no brain directed therapy was included (current treatment trials are exclusionary) Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||
Listed Location Countries ICMJE | Austria, Bulgaria, Canada, China, Croatia, France, Germany, Hong Kong, Hungary, Israel, Italy, Poland, Serbia, Spain, United States | ||||||||||||
Removed Location Countries | |||||||||||||
Administrative Information | |||||||||||||
NCT Number ICMJE | NCT02831959 | ||||||||||||
Other Study ID Numbers ICMJE | EF-25 METIS | ||||||||||||
Has Data Monitoring Committee | Yes | ||||||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||||||
IPD Sharing Statement ICMJE |
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Current Responsible Party | NovoCure Ltd. ( NovoCure GmbH ) | ||||||||||||
Original Responsible Party | NovoCure Ltd. | ||||||||||||
Current Study Sponsor ICMJE | NovoCure GmbH | ||||||||||||
Original Study Sponsor ICMJE | NovoCure Ltd. | ||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||
Investigators ICMJE |
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PRS Account | NovoCure Ltd. | ||||||||||||
Verification Date | March 2023 | ||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |