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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02336451




Registration number
NCT02336451
Ethics application status
Date submitted
8/01/2015
Date registered
13/01/2015

Titles & IDs
Public title
A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges
Scientific title
A Phase II, Multi-center, Open-label, Five-arm Study to Evaluate the Efficacy and Safety of Oral Ceritinib Treatment for Patients With ALK-positive Non-small Cell Lung Cancer (NSCLC) Metastatic to the Brain and/or to Leptomeninges
Secondary ID [1] 0 0
2014-000578-20
Secondary ID [2] 0 0
CLDK378A2205
Universal Trial Number (UTN)
Trial acronym
Ascend-7
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALK-positive Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ceritinib

Experimental: Arm 1 (PrALKi=Y, PrBRad=Y) - Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).

Experimental: Arm 2 (PrALKi=Y, PrBRad=N) - Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).

Experimental: Arm 3 (PrALKi=N, PrBRad=Y) - Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).

Experimental: Arm 4 (PrALKi=N, PrBRad=N) - Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).

Experimental: Arm 5 (LepDis) - Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.


Treatment: Drugs: Ceritinib
LDK378 is a gelatin capsule, administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule on an empty stomach.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) Per Investigator Assessment
Timepoint [1] 0 0
43 months
Secondary outcome [1] 0 0
Disease Control Rate (DCR) Per Investigator Assessment
Timepoint [1] 0 0
43 months
Secondary outcome [2] 0 0
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Investigator Assessment
Timepoint [2] 0 0
43 months
Secondary outcome [3] 0 0
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Blinded Independent Review Committee (BIRC) Assessment
Timepoint [3] 0 0
43 months
Secondary outcome [4] 0 0
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment at Weeks 8 & 16
Timepoint [4] 0 0
Week 8 and Week 16
Secondary outcome [5] 0 0
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment - Overall
Timepoint [5] 0 0
43 months
Secondary outcome [6] 0 0
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment at Weeks 8 & 16
Timepoint [6] 0 0
Week 8 and Week 16
Secondary outcome [7] 0 0
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment - Overall
Timepoint [7] 0 0
43 months
Secondary outcome [8] 0 0
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per Investigator Assessment
Timepoint [8] 0 0
43 months
Secondary outcome [9] 0 0
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per BIRC Assessment
Timepoint [9] 0 0
43 months
Secondary outcome [10] 0 0
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per Investigator Assessment
Timepoint [10] 0 0
43 months
Secondary outcome [11] 0 0
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per BIRC Assessment
Timepoint [11] 0 0
43 months
Secondary outcome [12] 0 0
Overall Extracranial Response Rate (OERR) Per RECIST 1.1 Per Investigator & BIRC Assessment
Timepoint [12] 0 0
43 months
Secondary outcome [13] 0 0
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment - Overall
Timepoint [13] 0 0
43 months
Secondary outcome [14] 0 0
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment at Weeks 8 & 16
Timepoint [14] 0 0
Week 8 and Week 16
Secondary outcome [15] 0 0
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per Investigator Assessment
Timepoint [15] 0 0
43 months
Secondary outcome [16] 0 0
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per BIRC Assessment
Timepoint [16] 0 0
43 months
Secondary outcome [17] 0 0
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per Investigator Assessment
Timepoint [17] 0 0
43 months
Secondary outcome [18] 0 0
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per BIRC Assessment
Timepoint [18] 0 0
43 months
Secondary outcome [19] 0 0
Overall Response Rate (ORR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Timepoint [19] 0 0
43 months
Secondary outcome [20] 0 0
Disease Control Rate (DCR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Timepoint [20] 0 0
43 months
Secondary outcome [21] 0 0
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
Timepoint [21] 0 0
43 months
Secondary outcome [22] 0 0
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Timepoint [22] 0 0
43 months
Secondary outcome [23] 0 0
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
Timepoint [23] 0 0
43 months
Secondary outcome [24] 0 0
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Timepoint [24] 0 0
43 months
Secondary outcome [25] 0 0
Progression Free Survival (PFS) (Whole Body) Per RECIST 1.1 Per Investigator & BIRC Assessment
Timepoint [25] 0 0
43 months
Secondary outcome [26] 0 0
Overall Survival (OS)
Timepoint [26] 0 0
24 weeks
Secondary outcome [27] 0 0
Pharmacokinetics (PK) of Ceritinib in Study Population: Cmax & Cmin (Trough)
Timepoint [27] 0 0
Cmax: Cycle 2 Day 1 (C2D1); Cmin: C1D1, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 - all 0hr (pre dose)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/02/2019
Sample size
Target
Accrual to date
Final
156
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Auckland
Recruitment postcode(s) [1] 0 0
- Auckland
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oklahoma
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Brazil
State/province [8] 0 0
Bahia
Country [9] 0 0
Brazil
State/province [9] 0 0
Rio Grande Do Sul
Country [10] 0 0
Brazil
State/province [10] 0 0
RN
Country [11] 0 0
Brazil
State/province [11] 0 0
SC
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Paulo
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
France
State/province [15] 0 0
Bouches Du Rhone
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Rennes
Country [18] 0 0
France
State/province [18] 0 0
Saint-Herblain Cédex
Country [19] 0 0
France
State/province [19] 0 0
Strasbourg Cedex
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Germany
State/province [21] 0 0
Bad Berka
Country [22] 0 0
Germany
State/province [22] 0 0
Koeln
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Pokfulam
Country [24] 0 0
Italy
State/province [24] 0 0
LI
Country [25] 0 0
Italy
State/province [25] 0 0
MB
Country [26] 0 0
Italy
State/province [26] 0 0
ME
Country [27] 0 0
Italy
State/province [27] 0 0
MI
Country [28] 0 0
Italy
State/province [28] 0 0
PG
Country [29] 0 0
Italy
State/province [29] 0 0
PN
Country [30] 0 0
Italy
State/province [30] 0 0
PR
Country [31] 0 0
Italy
State/province [31] 0 0
RM
Country [32] 0 0
Italy
State/province [32] 0 0
TO
Country [33] 0 0
Italy
State/province [33] 0 0
VR
Country [34] 0 0
Italy
State/province [34] 0 0
Napoli
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Korea
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Netherlands
State/province [37] 0 0
Amsterdam
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Saint Petersburg
Country [39] 0 0
Singapore
State/province [39] 0 0
Singapore
Country [40] 0 0
Spain
State/province [40] 0 0
Andalucia
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taiwan ROC
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
Turkey
State/province [45] 0 0
TUR
Country [46] 0 0
Turkey
State/province [46] 0 0
Ankara
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Surrey
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Birmingham
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02336451