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.
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
Drug | Synonyms | Arms |
---|
Ceritinib | | Ceritinib |
pemetrexed | | Chemotherapy |
docetaxel | | Chemotherapy |
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
Name | Type | Description | Interventions |
---|
Ceritinib | Experimental | Patients in this arm received 750 mg of ceritinib. | |
Chemotherapy | Active Comparator | Patients in this arm received chemotherapy of either pemetrexed or docetaxel as determined by BIRC. | |
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
Last Updated
May 7, 2021