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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
Sponsor:
Information provided by (Responsible Party):
NovoCure Ltd. ( NovoCure GmbH )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Brain Metastases From Non-small Cell Lung Cancer (NSCLC) Device: NovoTTF-200M device Other: Best Standard of Care Phase 3

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Study Design
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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) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC).
Study Start Date : July 2016
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: NovoTTF-200M device

NovoTTF-200M device Patients undergo SRS followed by continuous TTFields treatment using the NovoTTF-200M 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-200M 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
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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 following study treatments [ Time Frame: 3 years ]
  4. Time to second intracranial progression [ Time Frame: 3 years ]
  5. Time to intracranial progression, measured from the date of first SRS treatment to intracranial progression (per modified RECIST 1.1 Criteria) or neurological death, whichever occurs first. [ Time Frame: 3 years ]
  6. Time to first and second intracranial progression evaluated in two cohorts of patients, 1-4 brain metastases and 5-10 brain metastases. [ Time Frame: 3 years ]
  7. Rate of intracranial progression at 2, 4, 6, 8, 10, 12 months after first SRS treatment [ Time Frame: 3 years ]
  8. Time to distant progression, as measured from the date of first SRS treatment to a new intracranial lesion [ Time Frame: 3 years ]
  9. Rate of decline in cognitive function as measured by HVLT-R free recall, delayed recall and delayed recognition, COWAT and TMT Parts A and B at 2, 4, 6, 8, 10, 12 months follow-up. [ Time Frame: 3 years ]
  10. 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

  11. Quality of Life using the EORTC QLQ C30 with BN20 addendum [ Time Frame: 3 years ]
  12. Toxicity during NovoTTF-200M 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, Older Adult)
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).

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:

  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 study.
    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. Planned concurrent brain directed therapy (beyond SRS and NovoTTF-200M as per protocol)
Contacts and Locations
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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


Locations
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Sponsors and Collaborators
NovoCure GmbH
Investigators
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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
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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

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Responsible Party: NovoCure GmbH
ClinicalTrials.gov Identifier: NCT02831959    
Other Study ID Numbers: EF-25 METIS
First Posted: July 13, 2016    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by NovoCure Ltd. ( NovoCure GmbH ):
Non-Small Cell Lung Cancer
NSCLC
Brain metastases
Treatment
Minimal toxicity
TTFields
 TTF
Tumor Treating Fields
Novocure
SRS
Stereotactic radiosurgery
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
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