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An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

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. Identifier: NCT01964157
Recruitment Status : Unknown
Verified January 2019 by Yonsei University.
Recruitment status was:  Recruiting
First Posted : October 17, 2013
Last Update Posted : January 11, 2019
Information provided by (Responsible Party):
Yonsei University

Tracking Information
First Submitted Date  ICMJE October 9, 2013
First Posted Date  ICMJE October 17, 2013
Last Update Posted Date January 11, 2019
Actual Study Start Date  ICMJE September 1, 2013
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2013)
Overall response rate (ORR) [ Time Frame: 1 month after treatment ]
Lesions measurements are performed by CT or MRI scan, evaluation by RECIST criteria v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement
Official Title  ICMJE Not Provided
Brief Summary ROS1 is a receptor tyrosine kinase with constitutive kinase activity. ROS1 was previously discovered in cell lines where ROS1 fused with other proteins to act as a driver oncogene. In 2007, Rikova et al reported ROS1 fusion as driver mutations in NSCLC cell line (HCC78; SLC34A2-ROS1) and NSCLC patient (CD74-ROS1). Li et al also found about 1% of samples harboring CD74-ROS1 fusion in 202 resected lung adenocarcinomas from never smokers. The incidence was as high as 10% in East Asian population. Currently there are now at least 13 ROS1 fusion variants involving 8 fusion partners (CD74-, SLC34A2-, FIG-, TPM3-, SDC4-, LRIG3-, ERZ-, KDERL2-) identified in ROS1 positive NSCLC. LDK378 is an orally highly selective and potent ALK kinase inhibitor. In preclinical studies, LDK378 has much lower IC50 values than crizotinib in cell lines engineered to express ROS1 rearrangement (0.15 nM versus 3 nM) and is approximately 20-fold more potent. LDK378 is a potent inhibitor of tumor growth in rodent models of both ALCL and NSCLC. We suggest a phase II trial of LDK378 in advanced non-small cell lung cancer patients with ROS1 rearrangement. The aim of current trial is to evaluate the antitumor efficacy and safety profile of LDK378 and to identify biomarker to predict the tumor response to LDK378.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer (NSCLC)
Intervention  ICMJE Drug: LDK378
LDK378 750mg oral administration and continuously (28-day treatment schedule as one treatment cycle)
Study Arms  ICMJE Experimental: LDK378 arm
Intervention: Drug: LDK378
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 14, 2013)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with histologically or cytologically confirmed, unresectable NSCLC that carries a ROS1 rearrangement, as per FISH assay (Abbott Molecular Inc.)
  • ECOG performance status of 0 to 2
  • Male or female; ≥ 20 years of age
  • Subjects must have received at least 1 platinum doublet to treat their locally advanced or metastatic NSCLC
  • Subjects whose disease has progressed within 6 months Subjects with measurable lesion (using RECIST 1.1 criteria)
  • Subjects must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2
  • Subjects must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since
  • Provision of written informed consent prior to any study specific procedures

Exclusion Criteria:

  • Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
  • Any major operation or irradiation within 4 weeks of baseline disease assessment
  • Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
  • Subjects 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
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ or treated thyroid cancer.
  • Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
  • Pregnant or lactating female
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01964157
Other Study ID Numbers  ICMJE 4-2013-0237
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yonsei University
Study Sponsor  ICMJE Yonsei University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Yonsei University
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP