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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of metastatic NSCLC according to
the 7th edition of the AJCC Cancer Staging Manual. In addition, the NSCLC must harbor
an ALK rearrangement, as assessed using the FDA approved Vysis ALK Break Apart FISH
Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity
criteria). If documentation of ALK rearrangement as described above was not locally
available, a test to confirm ALK rearrangement was to be performed by a Novartis
designated central laboratory. Patients had to wait for the central laboratory result
of the ALK rearrangement status before initiating treatment with ceritinib
- At least one extracranial measurable lesion as defined by RECIST 1.1. A previously
irradiated site lesion could only be counted as a target lesion if there was clear
sign of progression since the irradiation.
- Patients could or could not have neurological symptoms but must have been able to
swallow and retain oral medication.
- Patients had to be neurologically stable within at least 1 week prior to the first
dose of study drug.
- Patients could have received prior chemotherapy, crizotinib (other ALK inhibitors were
not allowed), biologic therapy or other investigational agents.
- Patients must have recovered from all toxicities related to prior anticancer therapies
to grade = 1 (CTCAE v 4.03). Patients with any grade of alopecia were allowed to enter
the study.
- Patient had life expectancy = 6 weeks.
- Patient had a WHO performance status 0-2.
Patients in Arm 1 to 4 had to also meet the following inclusion criteria:
- Patients had to have active brain metastases from NSCLC, confirmed by Gadolinium-enhanced
MRI without concomitant leptomeningeal carcinomatosis. Dose of steroids had to be stable
for 5 days before the baseline brain MRI.
Patients in Arm 5 had to also meet the following inclusion criteria:
- Patients must have been diagnosed with leptomeningeal carcinomatosis.
Exclusion Criteria:
- Patients who needed whole brain radiation to control the brain metastases. Patients
were not eligible unless treated brain lesions were progressive or new brain lesions
were observed since the post whole brain radiation therapy MRI.
- Planning of any brain local treatment (including but not limited to surgery,
stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following
the administration of the first dose of study drug.
- Patient with a concurrent malignancy or history of a malignant disease other than
NSCLC that had been diagnosed and/or required therapy within the past 3 years.
Exceptions to this exclusion included the following: completely resected basal cell
and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Patient had impairment of GI function or GI disease that could significantly alter the
absorption of ceritinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
diarrhea, or malabsorption syndrome).
- Patient was receiving unstable or increasing doses of corticosteroids.
- Patient had other severe, acute, or chronic medical conditions including uncontrolled
diabetes mellitus or psychiatric conditions or laboratory abnormalities that in the
opinion of the investigator could increase the risk associated with study
participation, or that could interfere with the interpretation of study results.
Age minimum:
18 Years
Age maximum:
N/A
Gender:
All
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Secondary Outcome(s)
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Duration of Extracranial Response (DOER) Per RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment at Weeks 8 & 16
[Time Frame: Week 8 and Week 16]
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Disease Control Rate (DCR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Overall Survival (OS)
[Time Frame: 24 weeks]
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Progression Free Survival (PFS) (Whole Body) Per RECIST 1.1 Per Investigator & BIRC Assessment
[Time Frame: 43 months]
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Overall Extracranial Response Rate (OERR) Per RECIST 1.1 Per Investigator & BIRC Assessment
[Time Frame: 43 months]
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Overall Response Rate (ORR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment at Weeks 8 & 16
[Time Frame: Week 8 and Week 16]
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Duration of Extracranial Response (DOER) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment - Overall
[Time Frame: 43 months]
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Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment at Weeks 8 & 16
[Time Frame: Week 8 and Week 16]
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Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Blinded Independent Review Committee (BIRC) Assessment
[Time Frame: 43 months]
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Disease Control Rate (DCR) Per Investigator Assessment
[Time Frame: 43 months]
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Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment - Overall
[Time Frame: 43 months]
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Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment - Overall
[Time Frame: 43 months]
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Pharmacokinetics (PK) of Ceritinib in Study Population: Cmax & Cmin (Trough)
[Time Frame: Cmax: Cycle 2 Day 1 (C2D1); Cmin: C1D1, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 - all 0hr (pre dose)]
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Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Investigator Assessment
[Time Frame: 43 months]
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Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
[Time Frame: 43 months]
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