Clinical Trials /

LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

NCT01828112

Description:

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib
  • Official Title: A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib

Clinical Trial IDs

  • ORG STUDY ID: CLDK378A2303
  • SECONDARY ID: 2012-005637-36
  • NCT ID: NCT01828112

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
CeritinibCeritinib
pemetrexedChemotherapy
docetaxelChemotherapy

Purpose

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib.

Trial Arms

NameTypeDescriptionInterventions
CeritinibExperimentalPatients in this arm received 750 mg of ceritinib.
  • Ceritinib
ChemotherapyActive ComparatorPatients in this arm received chemotherapy of either pemetrexed or docetaxel as determined by BIRC.
  • pemetrexed
  • docetaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell
             lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by
             the FDA approved Abbott FISH Test.

          2. Patient has stage IIIB or IV diagnosis and must have received one or two prior
             regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of
             locally advanced or metastatic NSCLC.

          3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously
             irradiated site lesion may only be counted as a target lesion if there is clear sign
             of progression since the irradiation

          4. Patients must have received previous treatment with crizotinib for the treatment of
             locally advanced or metastatic NSCLC.

        Exclusion Criteria:

          1. Patient with known hypersensitivity to any of the excipients of LDK378
             (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and
             magnesium stearate)

          2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel
             or any known excipients of these drugs.

          3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically
             unstable or has required increasing doses of steroids within the 2 weeks prior to
             screening to manage CNS symptoms.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC)
Time Frame:'from the date of randomization to the date of first radiologically documented disease progression or death due to any cause up to approximately 24 months
Safety Issue:
Description:PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Month 18
Safety Issue:
Description:OS is defined as time from date of randomization to date of death due to any cause.
Measure:Overall Response Rate (ORR)
Time Frame:Month 18
Safety Issue:
Description:ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)
Measure:Duration of Response (DOR)
Time Frame:Month 18
Safety Issue:
Description:DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer
Measure:Disease Control Rate (DCR)
Time Frame:Month 18
Safety Issue:
Description:DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)
Measure:Time to Response (TTR)
Time Frame:Month 18
Safety Issue:
Description:TTR is defined as the time from date of randomization to date of first documented response (CR or PR)
Measure:Patient Reported Outcomes (PRO)
Time Frame:Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Safety Issue:
Description:
Measure:Time to Definitive Deterioration
Time Frame:from the date of randomization to the date of event for disease related symptoms
Safety Issue:
Description:
Measure:Overall Intracranial Response Rate (OIRR)
Time Frame:Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Safety Issue:
Description:OIRR is defined as the ORR based on lesions in brain (target, nontarget lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall confirmed response of CR or PR in the brain per modified RECIST 1.1* as assessed by BIRC neuroradiologist.
Measure:Intracranial Disease Control Rate (IDCR)
Time Frame:Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Safety Issue:
Description:IDCR is defined as the DCR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall response of CR or PR or SD (or non-CR/nonPD) in the brain per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.
Measure:Duration of Intracranial Response (DOIR)
Time Frame:Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Safety Issue:
Description:DOIR is defined as the DOR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated from the time of first documented response of CR or PR to the date of the first documented disease progression in the brain or death due to any cause per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non-Small Cell Lung Cancer
  • ALK
  • LDK378
  • Non-small cell lung carcinoma (NSCLC)
  • treatment of lung cancer after first metastasis
  • lung cancer
  • lung adenocarcinoma
  • Non small cell lung carcinoma
  • Non small cell lung cancer
  • NSCLC
  • chemotherapy
  • ALK-positive
  • ALK-rearranged advanced non-small cell lung cancer
  • crizotinib

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