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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: September 4, 2012
Last updated: August 31, 2016
Last verified: August 2016
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: 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    ORR (CR+PR) per RECIST 1.1 as assessed by BIRC

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

  • Progression-free survival (PFS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
    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 ]
    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 ]
    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
Study Completion Date: March 2016
Primary Completion Date: March 2016 (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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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 identifier: NCT01685060

  Show 52 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01685060     History of Changes
Other Study ID Numbers: CLDK378A2201
2012-003432-24 ( EudraCT Number )
Study First Received: September 4, 2012
Last Updated: August 31, 2016

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

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents processed this record on April 21, 2017