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LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01685060
First Posted: September 13, 2012
Last Update Posted: June 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined progressive disease (PD) as assessed by the investigator if, in the judgment of the investigator, there was evidence of clinical benefit. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator

Condition Intervention Phase
Non-Small Cell Lung Cancer Drug: LDK378 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Overall Response Rate (ORR) to LDK378 Per Investigator Assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.


Secondary Outcome Measures:
  • ORR Per Blinded Independent Review Committee (BIRC) Assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  • Duration of Response (DOR) by Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  • Duration of Response (DOR) by BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  • Disease Control Rate (DCR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.

  • Time to Response (TTR) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.

  • Time to Response (TTR) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.

  • Progression-free Survival (PFS) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.

  • Progression-free Survival (PFS) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.

  • Overall Intracranial Response Rate (OIRR) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.

  • Overall Intracranial Response Rate (OIRR) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.

  • Overall Survival (OS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.


Enrollment: 140
Actual Study Start Date: November 26, 2012
Study Completion Date: March 29, 2016
Primary Completion Date: March 29, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDK378
Patients treated with ceritinib/LDK378 750 mg once-daily, fasted
Drug: LDK378
Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).
Other Name: Ceritinib

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion critieria:

  • Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
  • Age 18 years or older at the time of informed consent.
  • Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
  • Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
  • Patients must have a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

Exclusion criteria:

  • Patients with known hypersensitivity to any of the excipients of LDK378.
  • Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
  • History of carcinomatous meningitis.
  • Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
  • Clinically significant, uncontrolled heart disease
  • Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01685060


  Hide Study Locations
Locations
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
United States, California
City of Hope National Medical Center Dept of Oncology 2
Duarte, California, United States, 91010-3000
University of California at Los Angeles Reg-5
Los Angeles, California, United States, 90095
University of California at San Diego, Moores Cancer Ctr SC
San Diego, California, United States, 92103
Stanford University Medical Center Stanford Cancer Center(2)
Stanford, California, United States, 94304
United States, Colorado
University of Colorado Hospital SC
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute Dept of Oncology
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medical Center SC
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center DeptofUofKansas CancerCenter-2
Kansas City, Kansas, United States, 66160
Cancer Center of Kansas Dept of CCK
Wichita, Kansas, United States, 67214-3728
United States, Maryland
Maryland Oncology Hematology, P.A. SC
Rockville, Maryland, United States, 20850
United States, Massachusetts
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States, 02114
United States, North Carolina
Levine Cancer Institute SC 1
Charlotte, North Carolina, United States, 28203
United States, Tennessee
Sarah Cannon Research Institute Drug Ship - 4
Nashville, Tennessee, United States, 37203
United States, Texas
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
Dallas, Texas, United States, 75390
United States, Washington
Seattle Cancer Care Alliance SC-1
Seattle, Washington, United States, 98105
United States, Wisconsin
University of Wisconsin Univ Wisc 2
Madison, Wisconsin, United States, 53792
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Novartis Investigative Site
Oshawa, Ontario, Canada, L1G 2B9
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site
Marseille cedex 20, France, 13915
Novartis Investigative Site
Paris, France, 75970
Germany
Novartis Investigative Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Novartis Investigative Site
Heidelberg, Germany, 69120
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Avellino, AV, Italy, 83100
Novartis Investigative Site
Livorno, LI, Italy, 57124
Novartis Investigative Site
Monza, MB, Italy, 20900
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Perugia, PG, Italy, 06129
Novartis Investigative Site
Parma, PR, Italy, 43100
Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 464-8681
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277-8577
Novartis Investigative Site
Akashi, Hyogo, Japan, 673-8558
Novartis Investigative Site
Okayama-city, Okayama, Japan, 700-8558
Novartis Investigative Site
OsakaSayama, Osaka, Japan, 589-8511
Novartis Investigative Site
Sunto-gun, Shizuoka, Japan, 411-8777
Novartis Investigative Site
Chuo-ku, Tokyo, Japan, 104-0045
Novartis Investigative Site
Koto, Tokyo, Japan, 135-8550
Novartis Investigative Site
Fukuoka, Japan, 811-1395
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03722
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Maastricht, Netherlands, 5800
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
La Coruna, Galicia, Spain, 15006
Novartis Investigative Site
Madrid, Spain, 28046
United Kingdom
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01685060     History of Changes
Other Study ID Numbers: CLDK378A2201
2012-003432-24 ( EudraCT Number )
First Submitted: September 4, 2012
First Posted: September 13, 2012
Results First Submitted: March 27, 2017
Results First Posted: May 8, 2017
Last Update Posted: June 19, 2017
Last Verified: May 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-Small Cell Lung Cancer
NSCLC
ALK
LDK378
Ceritinib

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Ceritinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents