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

Study Overview
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Brief Summary
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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. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Ceritinib
* Drug: pemetrexed
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. 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 Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC. Exclusion Criteria: Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate) Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceritinib<br>Patients in this arm received 750 mg of ceritinib. | Drug: Ceritinib<br>* Ceritinib is the investigational treatment and is referred to as the investigational study drug and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.<br>|
| Active Comparator: Chemotherapy<br>Patients in this arm received chemotherapy of either pemetrexed or docetaxel as determined by BIRC. | Drug: pemetrexed<br>* Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m2 every 21 days.<br>Drug: docetaxel<br>* Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m2 every 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC) | 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. | '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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as time from date of randomization to date of death due to any cause. | Month 18 | 
| Overall Response Rate (ORR) | ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR) | Month 18 | 
| Duration of Response (DOR) | 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 | Month 18 | 
| Disease Control Rate (DCR) | DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD) | Month 18 | 
| Time to Response (TTR) | TTR is defined as the time from date of randomization to date of first documented response (CR or PR) | Month 18 | 
| Patient Reported Outcomes (PRO) |  | Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks | 
| Time to Definitive Deterioration |  | from the date of randomization to the date of event for disease related symptoms | 
| Overall Intracranial Response Rate (OIRR) | 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. | Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks | 
| Intracranial Disease Control Rate (IDCR) | 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. | Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks | 
| Duration of Intracranial Response (DOIR) | 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. | Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crizotinib, 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