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.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: January 24, 2011
Last updated: May 13, 2015
Last verified: May 2015
This study will assess the safety and efficacy of LDK378 in adult patients with genetic abnormalities in anaplastic lymphoma kinase (ALK)

Condition Intervention Phase
Tumors Characterized by Genetic Abnormalities of ALK
Drug: LDK378
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 33 months ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment. A patient with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. MTD was determined at 750mg.

  • Overall Response Rate (ORR) Based on Investigator Assessment [ Time Frame: 33 months ] [ Designated as safety issue: No ]
    Overall response rate (ORR) is defined as the percentage of participants with a best overall complete response (CR) or partial response (PR) per RECIST 1.0. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI, CR is the disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Both CR and PR had to be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR = at least two determinations of CR, at least 4 weeks apart before progression. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR).

  • Duration of Response (DOR) Based on Investigator Assessment [ Time Frame: 33 months ] [ Designated as safety issue: No ]
    As per Kaplan-Meier estimate. Duration of response (DOR) is defined as the time from first documented response (partial response (PR) or complete response (CR)) to the date of first documented disease progression (PD) or death due to any cause, among patients with a confirmed PR or CR per RECIST 1.0.

Secondary Outcome Measures:
  • Type and Category of Study Drug Related Adverse Events [ Time Frame: 120 weeks ] [ Designated as safety issue: Yes ]
  • Absorption and Plasma Concentrations of LDK378 [ Time Frame: 120 weeks ] [ Designated as safety issue: No ]

Enrollment: 304
Study Start Date: January 2011
Estimated Study Completion Date: March 2016
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDK378: Arm 1A and Arm 1B
NSCLC patients previously treated with an ALK inhibitor
Drug: LDK378
LDK378 is a selective and a potent inhibitor of anaplastic lymphoma kinase (ALK) activity, is a capsule and is administered orally.
Experimental: LDK378: Arm 2
NSCLC patients not previously treated with an ALK inhibitor
Drug: LDK378
LDK378 is a selective and a potent inhibitor of anaplastic lymphoma kinase (ALK) activity, is a capsule and is administered orally.
Experimental: LDK378: Arm 3
Patients with other tumors that are ALK positive other than NSCLC
Drug: LDK378
LDK378 is a selective and a potent inhibitor of anaplastic lymphoma kinase (ALK) activity, is a capsule and is administered orally.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01283516

  Hide Study Locations
United States, Colorado
University of Colorado Colorado Univ
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center MSK
New York, New York, United States, 10021
United States, Pennsylvania
Fox Chase Cancer Center Fox Chase Cancer (2)
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, United States, 84103
United States, Washington
Seattle Cancer Care Alliance SC
Seattle, Washington, United States, 98109-1023
Australia, Victoria
Novartis Investigative Site
East Melbourne, Victoria, Australia, 3002
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Köln, Germany, 50937
Novartis Investigative Site
Ulm, Germany, 89081
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Singapore, Singapore, 169610
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
United Kingdom
Novartis Investigative Site
Glasgow, United Kingdom, G12 0YN
Novartis Investigative Site
Leicester, United Kingdom, LE1 5WW
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: May 13, 2015
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)

Keywords provided by Novartis:
ALK inhibitor,
genetic abnormalities

Additional relevant MeSH terms:
Congenital Abnormalities
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2015