Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01828099
Recruitment Status : Active, not recruiting
First Posted : April 10, 2013
Results First Posted : September 21, 2017
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 3, 2013
First Posted Date  ICMJE April 10, 2013
Results First Submitted Date  ICMJE June 23, 2017
Results First Posted Date  ICMJE September 21, 2017
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE March 13, 2013
Actual Primary Completion Date June 24, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2017)
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 (assessed every 6 weeks up to approximately 34 months) ]
PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2013)
Progression Free Survival (PFS) [ Time Frame: Month 33 ]
PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause
Change History Complete list of historical versions of study NCT01828099 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2017)
  • Overall Survival (OS) [ Time Frame: From randomization until death (up to approximately 34 months) ]
    OS defined as time from date of randomization to date of death due to any cause
  • Overall Response Rate (ORR) [ Time Frame: From randomization until death (up to approximately 34 months) ]
    ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: From randomization until death (up to approximately 34 months) ]
    DOR defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
  • Disease Control Rate (DCR) [ Time Frame: From randomization until death (up to approximately 34 months) ]
    DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD)
  • Time to Response (TTR) [ Time Frame: From randomization until death (up to approximately 34 months) ]
    TTR defined as the time from date of randomization to date of first documented response (CR or PR)
  • Patient Reported Outcomes [ Time Frame: Screening, followed by every 6 weeks until Month 33 after Month 33 every 9 weeks. ]
    The time to definitive deterioration from the date of randomization to the date of event for disease related symptoms.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2013)
  • Overall Survival (OS) [ Time Frame: Month 33 ]
    OS defined as time from date of randomization to date of death due to any cause
  • Overall Response Rate (ORR) [ Time Frame: Month 33 ]
    ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: Month 33 ]
    DOR 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
  • Disease Control Rate (DCR) [ Time Frame: Month 33 ]
    DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD)
  • Time to Response (TTR) [ Time Frame: Month 33 ]
    TTR defined as the time from date of randomization to date of first documented response (CR or PR)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
Official Title  ICMJE A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer
Brief Summary The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. Patients in the chemotherapy arm were allowed to cross-over to LDK378 after confirmed progressive disease (PD).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Ceritinib
    Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.
    Other Name: LDK378
  • Drug: Pemetrexed
    Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.
  • Drug: Cisplatin
    Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.
  • Drug: Carboplatin
    Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles
Study Arms  ICMJE
  • Experimental: Ceritinib
    Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state.
    Intervention: Drug: Ceritinib
  • Active Comparator: Chemotherapy
    Chemotherapy patients (Induction per Investigator's choice) were on four 21-day cycles of Pemetrexed 500mg/m2 iv + Cisplatin 75 mg/m2 or Pemetrexed 500 mg/m2 iv + Carboplatin AUC 5-6 iv followed by Pemetrexed 500 mg/m2 every 21 days followed by Pemetrexed maintenance in non-progressors, etc (other usual rule to stop treatment).
    Interventions:
    • Drug: Pemetrexed
    • Drug: Cisplatin
    • Drug: Carboplatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 24, 2017)
375
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2013)
348
Estimated Study Completion Date  ICMJE April 11, 2022
Actual Primary Completion Date June 24, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories.
  2. Patient has newly diagnosed stage IIIB (who are 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 exception of neo-adjuvant or adjuvant therapy
  3. Patient has at least one measurable lesion as defined by RECIST 1.1.

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 platinum containing drugs, pemetrexed 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico,   Argentina,   Australia,   Austria,   Brazil,   China,   Colombia,   Denmark,   France,   Germany,   Greece,   Hungary,   India,   Ireland,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Singapore,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom
Removed Location Countries Romania
 
Administrative Information
NCT Number  ICMJE NCT01828099
Other Study ID Numbers  ICMJE CLDK378A2301
2013-000319-26 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP