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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01685138
First received: September 4, 2012
Last updated: May 16, 2014
Last verified: May 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: 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 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


Enrollment: 126
Study Start Date: August 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
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: NCT01685138

  Hide Study Locations
Locations
United States, Massachusetts
Massachusetts General Hospital Mass Gen 5
Boston, Massachusetts, United States, 02114
United States, Texas
U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office
Dallas, Texas, United States, 75390-9151
Australia, New South Wales
Novartis Investigative Site
St. Leonards, New South Wales, Australia, 2065
Australia, Victoria
Novartis Investigative Site
Franston, Victoria, Australia, 3199
Australia
Novartis Investigative Site
Auckland, Australia, 1142
Belgium
Novartis Investigative Site
Genk, Belgium, 3600
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1Z6
Canada, Saskatchewan
Novartis Investigative Site
Saskatoon, Saskatchewan, Canada, S7N 4H4
France
Novartis Investigative Site
Saint Herblain cedex, France, 44805
Germany
Novartis Investigative Site
Essen, Germany, 45147
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
Genova, GE, Italy, 16132
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Novartis Investigative Site
Orbassano, TO, Italy, 10043
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
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, 738-736
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Norway
Novartis Investigative Site
Oslo, Norway, NO-0379
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 115478
Novartis Investigative Site
St-Petersburg, Russian Federation, 1970022
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Málaga, Andalucia, Spain, 29010
Novartis Investigative Site
Badalona, Catalunya, Spain, 08916
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Madrid, Spain, 28050
Novartis Investigative Site
Madrid, Spain, 28046
Sweden
Novartis Investigative Site
Stockholm, Sweden, SE-171 76
Taiwan
Novartis Investigative Site
Tainan 704, Taiwan ROC, Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Taichung, Taiwan, 407
Novartis Investigative Site
Taipei, Taiwan, 10002
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Songkla, Thailand, 90110
United Kingdom
Novartis Investigative Site
Colchester, United Kingdom, CO3 3NB
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: NCT01685138     History of Changes
Other Study ID Numbers: CLDK378A2203, 2012-003474-36
Study First Received: September 4, 2012
Last Updated: May 16, 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
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014