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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01283516




Registration number
NCT01283516
Ethics application status
Date submitted
24/01/2011
Date registered
26/01/2011

Titles & IDs
Public title
A Dose Escalation/Expansion Study of LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase
Scientific title
A Phase I, Multi-center, Open Label Dose Escalation Study of LDK378, Administered Orally in Adult Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase (ALK)
Secondary ID [1] 0 0
2010-019827-70
Secondary ID [2] 0 0
CLDK378X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tumors Characterized by Genetic Abnormalities of ALK 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LDK378

Experimental: LDK378 750 mg: Arm 1A and Arm 1B - NSCLC patients previously treated with an ALK inhibitor

Experimental: LDK378 750 mg: Arm 2 - NSCLC patients not previously treated with an ALK inhibitor

Experimental: LDK378 750 mg: Arm 3 - Patients with other tumors that are ALK positive other than NSCLC


Treatment: Drugs: LDK378
LDK378 is a selective and a potent inhibitor of anaplastic lymphoma kinase (ALK) activity, is a capsule and is administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
33 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) Based on Investigator Assessment
Timepoint [1] 0 0
275 weeks
Secondary outcome [2] 0 0
Overall Response Rate Based on Blinded Independent Review Committee (BIRC) Assessment
Timepoint [2] 0 0
275 weeks
Secondary outcome [3] 0 0
Duration of Response (DOR) Based on Investigator Assessment
Timepoint [3] 0 0
275 weeks
Secondary outcome [4] 0 0
Duration of Response (DOR) Based on BIRC
Timepoint [4] 0 0
275 weeks
Secondary outcome [5] 0 0
Progression-free Survival Based on Investigator Assessment
Timepoint [5] 0 0
275 weeks
Secondary outcome [6] 0 0
Progression-free Survival Based on BIRC Assessment
Timepoint [6] 0 0
275 weeks
Secondary outcome [7] 0 0
Primary Pharmacokinetics (PK) Parameter: AUC0-last
Timepoint [7] 0 0
PK run-in of Dose Escalation phase
Secondary outcome [8] 0 0
Primary Pharmacokinetics (PK) Parameter: AUC0-24h
Timepoint [8] 0 0
PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases
Secondary outcome [9] 0 0
Primary Pharmacokinetics (PK) Parameter: Tmax
Timepoint [9] 0 0
PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases
Secondary outcome [10] 0 0
Primary Pharmacokinetics (PK) Parameter: Cmax
Timepoint [10] 0 0
PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation ion phase, Cycle 2 Day 1 of dose escalation & expansion phases
Secondary outcome [11] 0 0
Secondary Pharmacokinetics (PK) Parameter: T1/2
Timepoint [11] 0 0
PK Run-in dose escalation phase
Secondary outcome [12] 0 0
Secondary Pharmacokinetics (PK) Parameter: CL/F
Timepoint [12] 0 0
PK Run-in dose escalation phase
Secondary outcome [13] 0 0
Secondary Pharmacokinetics (PK) Parameter: Vz/F
Timepoint [13] 0 0
PK Run-in dose escalation phase
Secondary outcome [14] 0 0
Secondary Pharmacokinetics (PK) Parameter: CLss/F
Timepoint [14] 0 0
Cycle 1 Day 8 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases
Secondary outcome [15] 0 0
Secondary Pharmacokinetics (PK) Parameter: Racc
Timepoint [15] 0 0
Cycle 1 Day 8 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases

Eligibility
Key inclusion criteria
* ECOG Performance Status of = 2 and life expectancy of = 12 weeks.
* Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
* For NSCLC, an ALK translocation must be detected by FISH in = 15% of tumor cells.
* In patients with diseases other than NSCLC, ALK translocation is not required and overexpression of ALK protein may be considered indicative of a genetic abnormality in ALK.
* Patients with measurable or non-measurable disease as determined by modified RECIST version 1.0 in dose-escalation phase, and patients with at least one measurable lesion as determined by RECIST 1.0 in expansion phase.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
* Patients with a prior or current history of a second malignancy, impaired GI function, history of pancreatitis or increased amylase or lipase, known diagnosis of HIV, and clinically significant cardiac disease were excluded.
* Patients treated with chemotherapy or biologic therapy or other investigational agent < 2 weeks prior to starting study drug for compounds with a half-life = 3 days, and < 4 weeks prior to starting study drug for compounds with a prolonged half-life were excluded.
* Further, patients treated with medications that were known to be strong inhibitors or inducers of CYP3A4/5 that could not be discontinued at least a week prior to start of treatment with LDK378 and for the duration of the study were also excluded.

Other protocol-defined inclusion/exclusion criteria may apply

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 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
24/01/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/05/2016
Sample size
Target
Accrual to date
Final
304
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
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah
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
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Germany
State/province [9] 0 0
Nordrhein-Westfalen
Country [10] 0 0
Germany
State/province [10] 0 0
Essen
Country [11] 0 0
Germany
State/province [11] 0 0
Heidelberg
Country [12] 0 0
Germany
State/province [12] 0 0
Ulm
Country [13] 0 0
Italy
State/province [13] 0 0
MI
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Korea
Country [15] 0 0
Netherlands
State/province [15] 0 0
Amsterdam
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore
Country [17] 0 0
Spain
State/province [17] 0 0
Catalunya
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Scotland
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Leicester

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)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01283516