Status:

UNKNOWN

A Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Lead Sponsor:

Yonsei University

Conditions:

Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Eligibility:

All Genders

20+ years

Phase:

PHASE2

Brief Summary

Lung cancer is the most leading cause of cancer-related mortality worldwide. Most of the patients with lung cancer are advanced stage at the time of diagnosis. The two oncogenes that are important in...

Detailed Description

Recently, our group found the prevalence of ROS1 rearrangement reached up to 3.2% in clinically selected population (never smokers) and 5% in genetically selected population (EGFR-/ALK-wild-type). The...

Eligibility Criteria

Inclusion

  • Inclusion criteria
  • histologically or cytologically confirmed, stage IV or recurrent NSCLC that carries a ROS1 rearrangement, as per anchored multiplex PCR
  • ECOG performance status of 0 to 2
  • Male or female≥ 20 years of age
  • treatment naive or may be allowed up to 2 prior systemic anti-cancer therapy for their stage IV or recurrent NSCLC, which includes cytotoxic chemotherapy and I-O, but excludes crizotinib.
  • measurable lesion (using RECIST 1.1 criteria)
  • measurable lesion (using RECIST 1.1 criteria)
  • archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since
  • Subjects who meet the following criteria:
  • ANC 1.5 x 109/L -Platelet 100 x 109/L
  • creatinine 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) 3 x ULN (If there is Liver Metastasis 5 x ULN
  • Total bilirubin 1.5 x ULN
  • written informed consent prior to any study specific procedures
  • Leptomeningeal carcinomatosis may be included
  • Exclusion criteria
  • More than two actionable mutations
  • Patients who received prior crizotinib 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 who have CNS complications that require urgent neurosurgical intervention(e.g. resection or shunt placement)
  • Other co-existing malignancies or malignancies diagnosed within the last 3 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
  • Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
  • Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation (see Appendix 1 Tables):
  • Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)
  • Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
  • Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
  • Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban).
  • Unstable or increasing doses of corticosteroids
  • enzyme-inducing anticonvulsive agents
  • herbal supplements
  • Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed.

Exclusion

    Key Trial Info

    Start Date :

    July 24 2018

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    October 1 2020

    Estimated Enrollment :

    46 Patients enrolled

    Trial Details

    Trial ID

    NCT03399487

    Start Date

    July 24 2018

    End Date

    October 1 2020

    Last Update

    January 11 2019

    Active Locations (1)

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    Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine

    Seoul, South Korea, 120-752

    A Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement | DecenTrialz