LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

This study is currently recruiting participants.
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01685138
First received: September 4, 2012
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

A single-arm, open-label, two-stage multicenter, phase II study. Patients will be pre-screened for ALK positive status. Treatment with LDK378 at 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 anticancer 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. 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. Male and female patients aged 18 or over with ALK-rearranged NSCLC will be screened for eligibility. Patients must have received no prior crizotinib, and must be chemotherapy-naïve or have been pretreated with cytotoxic chemotherapy (up to three prior lines)


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

Study Type: Interventional
Study Design: 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 Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

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 (OR) defined as complete response (CR) or partial response (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 Independent Review Committee) assessment

  • 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 assessment

  • 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 assessment

  • 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


Estimated Enrollment: 105
Study Start Date: December 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDK378
Oral LDK378 750 mg once daily
Drug: LDK378
Oral LDK378 750 mg once daily

  Show Detailed Description

  Eligibility

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

Inclusion criteria:

  • Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved Vysis ALK break-apart FISH assay (Abbott Molecular Inc.)
  • Age 18 years or older at the time of informed consent.
  • Patients must have NSCLC that has progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was received
  • Patients must be chemotherapy-naive or have received 1-3 lines of cytotoxic chemotherapy 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:

  • Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01685138

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Hide Study Locations
Locations
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp Recruiting
Fayetteville, Arkansas, United States, 72753
Contact: Holly Kinser    479-872-8130    hkinser@hogonc.com   
Principal Investigator: Eric S. Schaefer         
United States, California
University of California at Los Angeles UCLA - Santa Monica 2 Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Julian Blake    310-582-4066    jblake@mednet.ucla.edu   
Principal Investigator: Edward Garon         
University of California Irvine Dept of Hematology/Oncology Recruiting
Orange, California, United States, 92868
Contact: Lorene Kong    714-456-8549    lkong@uci.edu   
Principal Investigator: Ignatius Ou         
University of California at San Diego, Moores Cancer Ctr Dept. of MooresCancerCenter(2) Withdrawn
San Diego, California, United States, 92103
United States, Florida
University of Miami SC Recruiting
Miami, Florida, United States, 33136
Contact: Curshana Sanders    305-243-4624    c.sanders@med.miami.edu   
Principal Investigator: Mohammad Jahanzeb         
H. Lee Moffitt Cancer Center & Research Institute SC-3 Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Jeff L. Jorski    813-745-4625    jeff.jorski@moffitt.org   
Principal Investigator: Jhanelle Gray         
United States, Illinois
Rush University Medical Center SC-3 Withdrawn
Chicago, Illinois, United States, 60612
United States, Iowa
University of Iowa Hospitals & Clinics SC-2 Recruiting
Iowa City, Iowa, United States, 52242
Contact: Kristen Johnson    319-356-4797    kristen-johnson@uiowa.edu   
Principal Investigator: Taher AbuHejleh         
United States, Massachusetts
Massachusetts General Hospital Mass Gen 5 Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kate Parhiala       kparhiala@partners.org   
Principal Investigator: Alice Shaw         
United States, Missouri
Washington University School Of Medicine-Siteman Cancer Ctr Wash Uni Not yet recruiting
St. Louis, Missouri, United States, 63110
Contact: Sonia Kalathiveetil    314-362-6963    skalathi@DOM.wustl.edu   
Principal Investigator: Maria Q. Baggstrom         
United States, North Carolina
Levine Cancer Institute SC 1 Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Tamika McKenzie    704-355-2884    Tamika.Mckenzie@carolinashealthcare.org   
Principal Investigator: Kathryn Mileham         
United States, Ohio
Case Western Reserve SC - 2 Recruiting
Cleveland, Ohio, United States, 44106-5000
Contact: Ramon Adams    216-844-7405    Ramon.adams@uhhospitals.org   
Principal Investigator: Neelesh Sharma         
United States, Pennsylvania
University of Pennsylvania Medical Center SC Withdrawn
Philadephia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute Dept of Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Emily Angarole       Emily.angarole@scresearch.net   
Principal Investigator: David R. Spigel         
United States, Texas
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office Recruiting
Dallas, Texas, United States, 75390-9151
Contact: Lijun Chen    214-648-7097    Lijun.Chen@UTSouthwestern.edu   
Principal Investigator: Joan H. Schiller         
University of Texas/MD Anderson Cancer Center SC-9 Withdrawn
Houston, Texas, United States, 77030-4009
United States, Utah
University of Utah / Huntsman Cancer Institute SC Withdrawn
Salt Lake City, Utah, United States, 84103
United States, Washington
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research SC-1 Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Yelena Bruhkis    206-288-7487    jlograss@uw.edu   
Principal Investigator: Renato Martins         
United States, Wisconsin
University of Wisconsin / Paul P. Carbone Comp Cancer Center SC Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Denae Walters    608-262-8665    dmwalters@uwcarbone.wisc.edu   
Principal Investigator: Ticiana Leal         
Australia, New South Wales
Novartis Investigative Site Recruiting
St. Leonards, New South Wales, Australia, 2065
Australia, Victoria
Novartis Investigative Site Recruiting
Franston, Victoria, Australia, 3199
Novartis Investigative Site Not yet recruiting
Melbourne, Victoria, Australia, 3002
Belgium
Novartis Investigative Site Recruiting
Genk, Belgium, 3600
Novartis Investigative Site Recruiting
Gent, Belgium, 9000
Novartis Investigative Site Not yet recruiting
Leuven, Belgium, 3000
Novartis Investigative Site Recruiting
Liege, Belgium, 4000
Novartis Investigative Site Recruiting
Mons, Belgium, 7000
Canada, Ontario
Novartis Investigative Site Withdrawn
London, Ontario, Canada, N6A 4L6
Novartis Investigative Site Recruiting
Oshawa, Ontario, Canada, L1G 2B9
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z6
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1E2
Canada, Saskatchewan
Novartis Investigative Site Recruiting
Regina, Saskatchewan, Canada, S4T 7T1
Novartis Investigative Site Recruiting
Saskatoon, Saskatchewan, Canada, S7N 4H4
France
Novartis Investigative Site Not yet recruiting
Caen, France, 14033
Novartis Investigative Site Withdrawn
Creteil, France, 94000
Novartis Investigative Site Withdrawn
Marseille cedex 20, France, 13915
Novartis Investigative Site Withdrawn
Paris, France, 75015
Novartis Investigative Site Recruiting
Saint Herblain cedex, France, 44805
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Köln, Germany, 50924
Hong Kong
Novartis Investigative Site Recruiting
Hong Kong, Hong Kong
Italy
Novartis Investigative Site Recruiting
Avellino, AV, Italy, 83100
Novartis Investigative Site Recruiting
Genova, GE, Italy, 16132
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Novartis Investigative Site Recruiting
Orbassano, TO, Italy, 10043
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 464-8681
Novartis Investigative Site Recruiting
Kashiwa, Chiba, Japan, 277-8577
Novartis Investigative Site Recruiting
Akashi, Hyogo, Japan, 673-8558
Novartis Investigative Site Recruiting
Okayama-city, Okayama, Japan, 700-8558
Novartis Investigative Site Recruiting
OsakaSayama, Osaka, Japan, 589-8511
Novartis Investigative Site Recruiting
Sunto-gun, Shizuoka, Japan, 411-8777
Novartis Investigative Site Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Novartis Investigative Site Recruiting
Koto, Tokyo, Japan, 135-8550
Novartis Investigative Site Recruiting
Fukuoka, Japan, 811-1395
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 738-736
New Zealand
Novartis Investigative Site Recruiting
Auckland, New Zealand, 1142
Norway
Novartis Investigative Site Recruiting
Oslo, Norway, NO-0424
Russian Federation
Novartis Investigative Site Recruiting
Rostov-na-Donu, Russia, Russian Federation, 344037
Novartis Investigative Site Recruiting
Chelyabinsk, Russian Federation, 454087
Novartis Investigative Site Withdrawn
Kazan, Russian Federation, 420029
Novartis Investigative Site Recruiting
Moscow, Russian Federation, 115478
Novartis Investigative Site Not yet recruiting
Moscow, Russian Federation, 115478
Novartis Investigative Site Recruiting
St-Petersburg, Russian Federation, 1970022
Novartis Investigative Site Recruiting
St. Petersburg, Russian Federation, 197758
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Málaga, Andalucia, Spain, 29010
Novartis Investigative Site Recruiting
Badalona, Cataluña, Spain, 08916
Novartis Investigative Site Recruiting
Barcelona, Cataluña, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28046
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Sweden
Novartis Investigative Site Withdrawn
Gävle, Sweden, 801 87
Novartis Investigative Site Recruiting
Stockholm, Sweden, SE-171 76
Novartis Investigative Site Recruiting
Uppsala, Sweden, SE-751 85
Taiwan
Novartis Investigative Site Recruiting
Tainan 704, Taiwan ROC, Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site Recruiting
Taichung, Taiwan, 407
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Thailand
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10700
Novartis Investigative Site Recruiting
Bangkok, Thailand, 10400
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Bangkok, Thailand, 10330
Novartis Investigative Site Withdrawn
Chiang Mai, Thailand, 50200
Novartis Investigative Site Recruiting
Songkla, Thailand, 90110
United Kingdom
Novartis Investigative Site Not yet recruiting
Colchester, United Kingdom, CO3 3NB
Novartis Investigative Site Recruiting
London, United Kingdom, SE1 9RT
Novartis Investigative Site Recruiting
London, United Kingdom, WC1E 6HX
Novartis Investigative Site Withdrawn
Oxford, United Kingdom, OX3 7LJ
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: NCT01685138     History of Changes
Other Study ID Numbers: CLDK378A2203, 2012-003474-36
Study First Received: September 4, 2012
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
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
Norway: Norwegian Medicines Agency
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan: Center for Drug Evaluation
Thailand: Food and Drug Administration
New Zealand: Ministry of Health
Russia: Ministry of Health of the Russian Federation

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 April 17, 2014