A Dose Escalation/Expansion Study of LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01283516
First received: January 24, 2011
Last updated: July 18, 2014
Last verified: July 2014
Results First Received: May 29, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Tumors Characterized by Genetic Abnormalities of ALK
Intervention: Drug: LDK378

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 304 patients were treated with LDK378 in the study, including 59 patients from the dose-escalation phase (including 10 patients at 750 mg) and 245 patients from the expansion phase treated at LDK378 750 mg.

Reporting Groups
  Description
50 mg Participants receiving 50 mg of LDK378
100 mg Participants receiving 100 mg of LDK378
200 mg Participants receiving 200 mg of LDK378
300 mg Participants receiving 300 mg of LDK378
400 mg Participants receiving 400 mg of LDK378
500 mg Participants receiving 500 mg of LDK378
600 mg Participants receiving 600 mg of LDK378
700 mg Participants receiving 700 mg of LDK378
750 mg Participants receiving 750 mg of LDK378

Participant Flow:   Overall Study
    50 mg     100 mg     200 mg     300 mg     400 mg     500 mg     600 mg     700 mg     750 mg  
STARTED     2 [1]   2     3     3     14     10     10     5     255  
Non-Small Cell Lung Cancer (NSCLC)     2     1     2     3     12     10     9     5     246  
Dose-Determining Set (DDS)     2     1     3     3     14     8     10     5     8  
COMPLETED     0 [2]   0     1     0     1     2     2     2     133  
NOT COMPLETED     2     2     2     3     13     8     8     3     122  
Adverse Event                 0                 0                 0                 0                 0                 0                 2                 0                 24  
Death                 0                 0                 0                 0                 0                 1                 0                 1                 6  
Disease Progression                 2                 2                 2                 3                 12                 7                 6                 2                 81  
Withdrawal by Subject                 0                 0                 0                 0                 1                 0                 0                 0                 11  
[1] Started = Full Analysis Set and Safety Set
[2] Completed = Treatment Ongoing



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS) consisted of all patients (including NSCLC and non-NSCLC) who received at least one dose of LDK378. Patients were classified according to the intended treatment dose group.

Reporting Groups
  Description
50 mg Participants receiving 50 mg of LDK378
100 mg Participants receiving 100 mg of LDK378
200 mg Participants receiving 200 mg of LDK378
300 mg Participants receiving 300 mg of LDK378
400 mg Participants receiving 400 mg of LDK378
500 mg Participants receiving 500 mg of LDK378
600 mg Participants receiving 600 mg of LDK378
700 mg Participants receiving 700 mg of LDK378
750 mg Participants receiving 750 mg of LDK378
Total Total of all reporting groups

Baseline Measures
    50 mg     100 mg     200 mg     300 mg     400 mg     500 mg     600 mg     700 mg     750 mg     Total  
Number of Participants  
[units: participants]
  2     2     3     3     14     10     10     5     255     304  
Age  
[units: Years]
Mean ± Standard Deviation
  46.5  ± 23.33     30.5  ± 12.02     53.7  ± 10.69     58.7  ± 5.03     48.7  ± 15.62     55.0  ± 15.99     54.6  ± 13.22     56.4  ± 4.67     51.9  ± 12.08     52.0  ± 12.41  
Age, Customized  
[units: Participants]
                   
<65 years     2     2     2     3     12     7     7     5     215     255  
>=65 years     0     0     1     0     2     3     3     0     40     49  
Gender  
[units: Participants]
                   
Female     1     1     3     2     10     6     7     4     136     170  
Male     1     1     0     1     4     4     3     1     119     134  
Race/Ethnicity, Customized  
[units: Participants]
                   
Hispanic or Latino     0     0     1     0     0     1     3     1     26     32  
Chinese     0     0     0     0     1     1     0     0     17     19  
Indian (Indian subcontinent)     0     0     0     0     0     0     0     0     6     6  
Mixed Ethnicity     0     0     0     0     1     0     1     0     1     3  
Other     2     2     2     3     12     8     6     4     205     244  
Predominant Race  
[units: Participants]
                   
Caucasian     2     2     2     2     12     8     8     3     160     199  
Black     0     0     0     0     0     0     0     0     4     4  
Asian     0     0     0     1     2     2     2     1     87     95  
Native American     0     0     0     0     0     0     0     0     1     1  
Pacific Islander     0     0     1     0     0     0     0     0     0     1  
Other     0     0     0     0     0     0     0     1     3     4  
Weight  
[units: Kilograms¬†(kg)]
Mean ± Standard Deviation
  60.8  ± 19.80     67.8  ± 5.94     69.2  ± 17.20     54.1  ± 9.70     69.2  ± 15.91     72.2  ± 18.74     63.8  ± 13.23     61.6  ± 16.05     69.2  ± 15.64     68.8  ± 15.61  
Height  
[units: centimenters¬†(cm)]
Mean ± Standard Deviation
  169.0  ± 7.07     178.0  ± 14.14     161.3  ± 3.04     164.6  ± 5.82     169.9  ± 9.35     166.4  ± 12.24     165.1  ± 8.67     163.6  ± 5.05     167.5  ± 9.87     167.5  ± 9.78  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  21.1  ± 5.16     21.8  ± 5.30     26.5  ± 5.69     20.2  ± 5.08     24.0  ± 5.38     25.9  ± 5.41     23.1  ± 2.78     24.3  ± 6.06     24.5  ± 4.40     24.4  ± 4.48  
WHO/ECOG Performance status [1]
[units: Participants]
                   
0:Fully active,in line with pre-disease activities     1     1     1     0     3     2     2     1     65     76  
1: Able to carry out light work     1     1     2     3     8     7     7     3     161     193  
2:Capable of self-care up & about >50% of the time     0     0     0     0     3     1     1     1     28     34  
3: Limited self-care, confined to bed/chair >50%     0     0     0     0     0     0     0     0     1     1  
Smoking History  
[units: Participants]
                   
Never Smoked     2     1     1     2     9     7     8     3     159     192  
Ex-Smoker     0     1     2     1     5     3     2     2     88     104  
Current Smoker     0     0     0     0     0     0     0     0     8     8  
[1] The ECOG performance status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.



  Outcome Measures
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1.  Primary:   Number of Participants With Dose Limiting Toxicities (DLTs)   [ Time Frame: 33 months ]

2.  Primary:   Overall Response Rate (ORR) Based on Investigator Assessment   [ Time Frame: 33 months ]

3.  Primary:   Duration of Response (DOR) Based on Investigator Assessment   [ Time Frame: 33 months ]

4.  Secondary:   Type and Category of Study Drug Related Adverse Events   [ Time Frame: 120 weeks ]
Results not yet posted.   Anticipated Posting Date:   06/2016   Safety Issue:   Yes

5.  Secondary:   Absorption and Plasma Concentrations of LDK378   [ Time Frame: 120 weeks ]
Results not yet posted.   Anticipated Posting Date:   06/2016   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01283516     History of Changes
Other Study ID Numbers: CLDK378X2101, 2010-019827-70
Study First Received: January 24, 2011
Results First Received: May 29, 2014
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Ministerio de Sanidad y Politico Social-Agencia Espanola de Medicamentos y Productos Sanitarios
Germany:The Federal Institute for Drugs and Medical Devices (BfArM)
Belgium: Federal Agency for Medicinal Products and Health Products
The Netherlands: Dutch Healthcare Inspectorate (IGZ)
Italy: Ministry of Labor, Health & Social Affairs, Department of Innovation
Australia: Therapeutic Goods Administration
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration (KFDA)