LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: LDK378
Intervention description: Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).
Intervention MeSH terms: Ceritinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; NSCLC; ALK; LDK378; Ceritinib

Summary:

      A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd
      continued until the patient experienced unacceptable toxicity that precluded further
      treatment, discontinued treatment at the discretion of the investigator or patient, started a
      new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined
      progressive disease (PD) as assessed by the investigator if, in the judgment of the
      investigator, there was evidence of clinical benefit. In these patients tumor assessment
      would continue as per the schedule of assessments until treatment with LDK378 was permanently
      discontinued. Patients who discontinued the study medication in the absence of progression
      continued to be followed for tumor assessment until the time of PD as assessed by the
      investigator
    

Eligibility criteria:

        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.