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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01685060
First received: September 4, 2012
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd will continue until the patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anti-cancer therapy and/or dies. LDK378 may be continued beyond RECIST-defined PD as assessed by the investigator if, in the judgment of the investigator, there is evidence of clinical benefit. In these patients tumor assessment should continue as per the schedule of assessments until treatment with LDK378 is permanently discontinued. Patients who discontinue the study medication in the absence of progression will continue 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: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:

Primary Outcome Measures:
  • Overall response rate (ORR) to LDK378 by investigator assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator


Secondary Outcome Measures:
  • Duration of response (DOR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    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 investigator and BIRC (Blinded Imaging Review Committee)

  • Disease control rate (DCR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC

  • Time to Response (TTR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC

  • ORR by BIRC assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    ORR (CR+PR) per RECIST 1.1 as assessed by BIRC

  • Safety profile [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: Yes ]
    Adverse events and laboratory abnormalities

  • Progression-free survival (PFS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment

  • Overall survival (OS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    OS, defined as time from first dose of LDK378 to death due to any cause

  • Overall intracranial response rate (OIRR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline


Enrollment: 141
Study Start Date: November 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDK378
Oral LDK378 750 mg once daily
Drug: LDK378
Other Name: Oral LDK378 750mg once daily

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT01685060

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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 UCLA - Santa Monica 2
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 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, 60546
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
Associates in Oncology/Hematology, P.C. 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 Dept of Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
Dallas, Texas, United States, 75390-9151
United States, Washington
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research SC-1
Seattle, Washington, United States, 98109-1023
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
Heidelberg, Germany, 69120
Novartis Investigative Site
Köln, Germany, 50924
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, 110 744
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 135-710
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

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01685060     History of Changes
Other Study ID Numbers: CLDK378A2201, 2012-003432-24
Study First Received: September 4, 2012
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
Italy: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Non-Small Cell Lung Cancer, ALK, LDK378

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 26, 2014