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Effect of TTFields (150 kHz) in Non-small Cell Lung Cancer (NSCLC) Patients With 1-10 Brain Metastases Following Radiosurgery (METIS)

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ClinicalTrials.gov Identifier: NCT02831959
Recruitment Status : Recruiting
First Posted : July 13, 2016
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
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 1-10 brain metastases, treated with NovoTTF-100M 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.

Condition or disease Intervention/treatment Phase
Brain Metastases From Non-small Cell Lung Cancer (NSCLC) Device: NovoTTF-100M device Other: Best Standard of Care Phase 3

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Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pivotal, Open-label, Randomized Study of Radiosurgery With or Without Tumor Treating Fields (TTFields) (150kHz) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC)
Study Start Date : July 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: NovoTTF-100M device
Patients undergo SRS followed by continuous TTFields treatment using the NovoTTF-100M device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.
Device: NovoTTF-100M device Other: Best Standard of Care
Active Comparator: Best Standard of Care
Patients will undergo SRS alone and be treated with the best known standard of care for Non-Small Cell Lung Cancer metastatic to the brain.
Other: Best Standard of Care


Outcome Measures

Primary Outcome Measures :
  1. Time to intracranial progression [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Time to neurocognitive failure [ Time Frame: 3 years ]
    Measured by cognitive decline on a battery of tests: Hopkins Verbal Learning Test (HVLT-R) free recall, delayed recall, and delayed recognition; Controlled Oral Word Association Test (COWAT); and Trail Making Tests (TMT) Parts A and B

  2. Overall survival [ Time Frame: 3 years ]
  3. Radiological response in the brain [ Time Frame: 3 years ]
  4. Time to second intracranial progression [ Time Frame: 3 years ]
  5. Time to first and second intracranial progression evaluated in two cohorts, 1-4 brain metastases and 5-10 brain metastases. [ Time Frame: 3 years ]
  6. Rate of intracranial progression at 2, 4, 6, 8, 10, 12 months [ Time Frame: 3 years ]
  7. Time to distant progression [ Time Frame: 3 years ]
  8. Rate of decline in cognitive function at 2, 4, 6, 8, 10, 12 months [ Time Frame: 3 years ]
    Measured by HVLT-R free recall, delayed recall, and delayed recognition; COWAT; and TMT Parts A and B

  9. Neurocognitive failure-free survival [ Time Frame: 3 years ]
    Defined from the date of first SRS treatment to neurocognitive failure (as measured by HVLT-R free recall, delayed recall, and delayed recognition; COWAT; and TMT Parts A and B) or death (whichever occurs first), censored at the last neurocognitive assessment on which the patient was reported alive without neurocognitive failure

  10. Quality of Life using the EORTC QLQ C30 with BN20 addendum [ Time Frame: 3 years ]
  11. Toxicity during NovoTTF-100M treatment based on incidence and severity of treatment emergent adverse events as evaluated using the CTCAE version 4.0 [ Time Frame: 3 years ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years of age and older
  2. Life expectancy of ≥ 3 months
  3. New diagnosis of brain metastases from a histologically or cytologically confirmed primary or metastatic NSCLC tumor within 5 years of registration on the study. If the original histological proof of malignancy is greater than 5 years, then pathological confirmation is required (i.e.: from extra-cranial or intracranial disease).
  4. Karnofsky performance status (KPS) ≥ 70
  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:

    1. largest tumor volume < 10 cc
    2. longest tumor diameter < 3 cm
    3. Cumulative volume of all tumors ≤ 15 cc
  6. At least one measurable lesion per RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) Criteria for brain metastasis
  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-100M 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:

  1. Patients who are known to have somatic tumor mutations in the following genes, for which targeted agents are available that directly affect the treatment of brain metastasis: Anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), ROS-1 proto-oncogene, and proto-oncogene B-RAF
  2. Patients who have a single, operable brain metastasis
  3. Patients with significant edema leading to risk of brain herniation
  4. Patients with midline shift > 10mm
  5. Patients with intractable seizures
  6. Leptomeningeal metastases
  7. Recurrent brain metastases
  8. Prior WBRT for newly diagnosed brain metastases
  9. Severe comorbidities:

    1. Clinically-significant inadequate hematological, hepatic and renal function, defined as: Neutrophil count < 1.5 x 10 9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) > 2.5 x ULN or > 5 x ULN if patient has documented liver metastases; and serum creatinine > 1.5 x ULN
    2. History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
    3. History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial.
    4. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable
    5. Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
    6. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
  10. Implantable electronic medical devices in the brain
  11. Known allergies to medical adhesives or hydrogel
  12. Currently pregnant or breastfeeding
  13. Concurrent brain directed therapy (beyond SRS and NovoTTF-100M as per protocol)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02831959


Contacts
Contact: Lori A. Ladd patientinfo@novocure.com

  Show 63 Study Locations
Sponsors and Collaborators
NovoCure Ltd.
Investigators
Principal Investigator: Minesh Mehta, MD Miami Cancer Institute, Miami FL USA
Principal Investigator: Paul Brown, MD MD Anderson Cancer Center, Houston TX USA
Principal Investigator: Vinai Gondi, MD Northwestern Medicine Cancer Center, Warenville IL USA
Principal Investigator: Manmeet Ahluwalia, MD Cleveland Clinic, Cleveland OH USA
More Information

Publications:
Brozova H, Lucas A, Salmaggi A, Vymazal J. COMET: A phase II randomized study of TTFields versus supportive care in non-small cell lung cancer patients with 1-5 brain metastases - initial safety results. Neuro Oncol. 2015 Nov; 17 (suppl 5): v46. doi:10.1093/neuonc/nov208.6

Responsible Party: NovoCure Ltd.
ClinicalTrials.gov Identifier: NCT02831959     History of Changes
Other Study ID Numbers: EF-25
First Posted: July 13, 2016    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by NovoCure Ltd.:
Non-Small Cell Lung Cancer
NSCLC
Brain metastases
Treatment
Minimal toxicity
TTFields
TTF
Tumor Treating Fields
Novocure
SRS
Stereotactic radiosurgery

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases