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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01772797




Registration number
NCT01772797
Ethics application status
Date submitted
17/01/2013
Date registered
21/01/2013
Date last updated
19/12/2020

Titles & IDs
Public title
Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer
Scientific title
A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer
Secondary ID [1] 0 0
2012-004632-29
Secondary ID [2] 0 0
CLDK378X2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Lymphoma Kinase (ALK) 0 0
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 - LDK378
Treatment: Drugs - AUY922

Experimental: LDK378 and AUY922 -


Treatment: Drugs: LDK378
LDK378 is a capsule to be taken daily by mouth.

Treatment: Drugs: AUY922
AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence rate of Dose Limiting Toxicities (DLT)
Timepoint [1] 0 0
up to day 28 after the patient's first dose
Secondary outcome [1] 0 0
Number of patients with adverse events
Timepoint [1] 0 0
30 months
Secondary outcome [2] 0 0
Changes in laboratory values
Timepoint [2] 0 0
30 months
Secondary outcome [3] 0 0
Assessments of electrocardiograms
Timepoint [3] 0 0
30 months
Secondary outcome [4] 0 0
Assessments of dose interruptions, reductions, and dose intensity
Timepoint [4] 0 0
30 months
Secondary outcome [5] 0 0
Plasma PK parameter of LDK378 and AUY922: Tmax
Timepoint [5] 0 0
30 months
Secondary outcome [6] 0 0
Overall response rate (ORR)
Timepoint [6] 0 0
30 months
Secondary outcome [7] 0 0
Duration of Response (DoR)
Timepoint [7] 0 0
30 months
Secondary outcome [8] 0 0
Time to Response (TTR)
Timepoint [8] 0 0
30 months
Secondary outcome [9] 0 0
Progression free survival (PFS)
Timepoint [9] 0 0
30 months
Secondary outcome [10] 0 0
Number of patients with serious adverse events
Timepoint [10] 0 0
30 months
Secondary outcome [11] 0 0
Plasma PK parameter of LDK378 and AUY922: Cmax
Timepoint [11] 0 0
30 months
Secondary outcome [12] 0 0
Plasma PK parameter of LDK378 and AUY922: AUClast
Timepoint [12] 0 0
30 months
Secondary outcome [13] 0 0
Plasma PK parameter of LDK378 and AUY922: AUCtau
Timepoint [13] 0 0
30 months
Secondary outcome [14] 0 0
Plasma PK parameter of LDK378 and AUY922: Cmin
Timepoint [14] 0 0
30 months
Secondary outcome [15] 0 0
Plasma PK parameter of LDK378 and AUY922: Racc
Timepoint [15] 0 0
30 months

Eligibility
Key inclusion criteria
* locally advanced or metastatic NSCLC that has progressed during or following therapy with an ALK inhibitor
* tumor must carry an ALK rearrangement in 15% or more of tumor cells as measured by FISH
* disease that can be evaluated by RECIST v1.1 and measurable disease
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* central nervous system (CNS) metastases that are symptomatic or require increasing steroids or CNS-directed therapy to control CNS disease
* history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
* clinically significant cardiac dysfunction
* inadequate end organ function as defined by specified laboratory values
* use of medications known to be strong inhibitors or inducters of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment
* use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment
* clinically significant, uncontrolled impaired gastrointestinal function or GI disease
* prior treatment with a HSP90 inhibitor
* radiotherapy to lung within 4 weeks prior to the first dose of study treatment or patients who have not recovered from radiotherapy-related toxicities
* pregnant or nursing women
* history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
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
1/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2016
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Utah
Country [5] 0 0
Italy
State/province [5] 0 0
MI
Country [6] 0 0
Singapore
State/province [6] 0 0
Singapore
Country [7] 0 0
Spain
State/province [7] 0 0
Catalunya

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer.
Trial website
https://clinicaltrials.gov/study/NCT01772797
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01772797