TriangleNCT01828099 · CITED IN SOURCE DOCUMENTS
LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-01-16
To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)
Overall Survival (OS)
Overall Response Rate (ORR) by BIRC Assessment
Overall Response Rate (ORR) by Investigator Assessment
Duration of Response (DOR) by BIRC Assessment
Duration of Response (DOR) by Investigator Assessment
Disease Control Rate (DCR) by BIRC Assessment
Disease Control Rate (DCR) by Investigator Assessment
Time to Response (TTR) by BIRC Assessment
Time to Response (TTR) by Investigator Assessment
PFS by Investigator Assessment
Overall Intracranial Response Rate (OIRR)
Intracranial Disease Control Rate (IDCR)
Duration of Intracranial Response (DOIR)
Time to Definitive 10 Point Deterioration in the Composite Endpoint of Pain, Cough or Dyspnea in the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ)- Lung Cancer (LC) 13 Questionnaire
Time to Definitive Deterioration in the Composite Endpoint of Pain, Cough or Dyspnea in the Lung Cancer Symptom Scale (LCSS)
Least Squares Mean Scores on the EORTC-QLQ C30
Least Squares Mean Scores on the EORTC QLQ- LC13
Least Squares Mean Scores on the Lung Cancer Symptom Scale (LCSS)
Least Squares Mean Scores on the EQ-5D-5L Index
Least Squares Mean Scores on the EQ-5D-5L Visual Analogue Score (VAS)
Cmax of LDK378
Tmax of LDK378
Tlast of LDK378
AUC0-24 of LDK378
All Collected Deaths
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Key Inclusion Criteria: 1. The patient had a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that was Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test was performed at Novartis designated central laboratories. 2. The patient had a newly diagnosed stage IIIB (who was not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with the exception of neo-adjuvant or adjuvant therapy. 3. The patient had at least one measurable lesion as defined by RECIST 1.1. Key Exclusion Criteria: 1. The patient had known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide, and magnesium stearate). 2. The patient had a history of severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs. 3. The patient had symptomatic central nervous system (CNS) metastases and was neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.
- healthy Volunteers
- false
- maximum Age
- 100 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state.
- intervention Names
- Drug: Ceritinib
- label
- Ceritinib
- type
- EXPERIMENTAL
- description
- Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance)
- intervention Names
- Drug: Pemetrexed
- Drug: Cisplatin
- Drug: Carboplatin
- label
- Chemotherapy
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Ceritinib
- description
- Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule.
- name
- Ceritinib
- other Names
- LDK378
- type
- DRUG
- arm Group Labels
- Chemotherapy
- description
- Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle
- name
- Pemetrexed
- type
- DRUG
- arm Group Labels
- Chemotherapy
- description
- Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles.
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Chemotherapy
- description
- Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles
- name
- Carboplatin
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 376
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by BIRC per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the Kaplan-Meier (KM) method.
- measure
- Progression Free Survival (PFS) by 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 34 months
- secondary Outcomes
- description
- OS defined as time from date of randomization to date of death due to any cause. If the patient was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cut-off date. The distribution of OS was estimated using the KM method.
- measure
- Overall Survival (OS)
- time Frame
- From date of randomization to date of death due to any cause, up to approximately 120 months
- description
- ORR is defined as the percentage of patients with a best overall response defined as complete response (CR) or or partial response (PR) measured by BIRC per RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- measure
- Overall Response Rate (ORR) by BIRC Assessment
- time Frame
- Up to approximately 34 months
- description
- ORR is defined as the percentage of patients with a best overall response defined as complete response (CR) or or partial response (PR) measured by investigator assessment per RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- measure
- Overall Response Rate (ORR) by Investigator Assessment
- time Frame
- Up to approximately 120 months
- description
- DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression (measured by BIRC assessment per RECIST 1.1) or death due to any cause. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a patient had not had an event, DOR was censored at the date of last adequate tumor assessment. Patients who had never achieved a best overall response of CR or PR were excluded from the analysis. The distribution function of DOR was estimated using the KM method.
- measure
- Duration of Response (DOR) by BIRC Assessment
- time Frame
- From first documented response to first documented disease progression or death, assessed up to approximately 34 months
- description
- DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression (measured by investigator assessment per RECIST 1.1) or death due to any cause. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a patient had not had an event, DOR was censored at the date of last adequate tumor assessment. Patients who had never achieved a best overall response of CR or PR were excluded from the analysis. The distribution function of DOR was estimated using the KM method.
- measure
- Duration of Response (DOR) by Investigator Assessment
- time Frame
- From first documented response to first documented disease progression or death, assessed up to approximately 120 months
- description
- DCR is defined as the percentage of patients with best overall response of CR, PR, or stable disease (SD) measured by BIRC assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
- measure
- Disease Control Rate (DCR) by BIRC Assessment
- time Frame
- Up to approximately 34 months
- description
- DCR is defined as the percentage of patients with best overall response of CR, PR, or stable disease (SD) measured by investigator assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
- measure
- Disease Control Rate (DCR) by Investigator Assessment
- time Frame
- Up to approximately 120 months
- description
- TTR is defined as the time from date of randomization to date of first documented response (CR or PR) measured by BIRC assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Patients who had not achieved a confirmed CR or PR were censored at the last adequate tumor assessment date when they had not had a PFS event or at maximum follow-up when they had had a PFS event.
- measure
- Time to Response (TTR) by BIRC Assessment
- time Frame
- From randomization to date of first documented response, up to approximately 34 months
- description
- TTR is defined as the time from date of randomization to date of first documented response (CR or PR) measured by investigator assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Patients who had not achieved a confirmed CR or PR were censored at the last adequate tumor assessment date when they had not had a PFS event or at maximum follow-up when they had had a PFS event
- measure
- Time to Response (TTR) by Investigator Assessment
- time Frame
- From randomization to date of first documented response, up to approximately 120 months
- description
- PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by investigator assessment per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the KM method.
- measure
- PFS by Investigator Assessment
- 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 120 months
- description
- OIRR is defined as the ORR based on lesions in brain (target, non-target lesions and new lesions, if applicable) and calculated as the percentage 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. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- measure
- Overall Intracranial Response Rate (OIRR)
- time Frame
- Up to approximately 34 months
- 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 percentage 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. CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease
- measure
- Intracranial Disease Control Rate (IDCR)
- time Frame
- Up to approximately 34 months
Full study description
- brief Summary
- To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.
- detailed Description
- This was an open-label, randomized, global, Phase III study that compared the efficacy and safety of ceritinib to standard first-line chemotherapy in patients with advanced (NSCLC) harboring ALK rearrangement. The confirmation of ALK rearrangement was done using the ICH test by a Novartis designated central laboratory. Prior to the study, patients had not received any previous systemic, anti-cancer therapy, including ALK inhibitors, for newly diagnosed advanced non-squamous NSCLC. The patients were randomized in a 1:1 ratio to either receive ceritinib (750 mg once daily, fasted) or chemotherapy. The chemotherapy regimen consisted of a platinum-based doublet with pemetrexed followed by pemetrexed maintenance in patients without progressive disease after 4 cycles. Treatment was continued until the blinded independent review committee (BIRC) confirmed disease progression based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), occurrence of unacceptable toxicity, or meeting other discontinuation criteria. Patients in either arm were permitted to continue the assigned study treatment beyond BIRC-confirmed disease progression in case of continued clinical benefit, as determined by the Investigator. All patients who discontinued treatment during the treatment phase for reasons other than death, lost to follow-up, pregnancy or disease progression entered the post-treatment follow-up period until disease progression, withdrawal of consent or death. In the chemotherapy arm, patients were allowed to switch and receive ceritinib after BIRC-confirmed disease progression (extension-treatment period).
Source references
- references
- citation
- Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. doi: 10.1016/S0140-6736(17)30123-X. Epub 2017 Jan 24.
- pmid
- 28126333
- type
- DERIVED
- citation
- Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.
- pmid
- 27130468
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-4d62c118d52425f329df
- requested nct id
- NCT01828099
- primary nct id
- NCT01828099
- source kind
- fda_spl_label
- source record id
- 8c405b95-6d3c-4bc5-9b01-2feb80903756
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- payload sha256
- 60f86f5a4c36ecb48afd7db4444c99aca2f2e464a0b70eaf324791e35b110d88
- payload
- application numbers
- NDA211225
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-4d62c118d52425f329df
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT01828099
- occurrences
- context exact
- who had not received prior systemic therapy for metastatic disease was evaluated in an open-label, randomized, active-controlled, multicenter study (ASCEND-4, NCT01828099). Patients were required to have World Health Organization (WHO) performance status 0-2 and ALK-positive NSCLC as identified by the VENTANA ALK (D5F3) CDx Assa
- end
- 430
- exact text
- NCT01828099
- start
- 419
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00500.json
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- source json pointer
- /results/19/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 8c405b95-6d3c-4bc5-9b01-2feb80903756
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 7a40c245cc91c150a101b5668f578579e27334ea31dd4abe55007194f33aae1d
- spl effective time
- 20251215
- spl set id
- fff5d805-4ffd-4e8e-8e63-6f129697563e
Preserved source evidence · Not medical advice