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

• ClinicalTrials.gov Identifier: NCT01828099
• Recruitment Status: Completed
• First Posted: April 10, 2013
• Results First Posted: September 21, 2017
• Last Update Posted: January 24, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: April 3, 2013
• First Posted Date: April 10, 2013
• Results First Submitted Date: June 23, 2017
• Results First Posted Date: September 21, 2017
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: July 9, 2013
• Actual Primary Completion Date: June 24, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
• Official Title: 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 given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• 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

• 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 *

• 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. Erratum In: Lancet. 2017 Mar 4;389(10072):908.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 21, 2020): 376
• Original Estimated Enrollment (submitted: April 9, 2013): 348
• Actual Study Completion Date: January 7, 2024
• Actual Primary Completion Date: June 24, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Brazil, China, Colombia, Denmark, France, Germany, Greece, India, Ireland, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom
• Removed Location Countries: Argentina, Hungary, Portugal, Romania

Administrative Information

• NCT Number: NCT01828099
• Other Study ID Numbers: 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

• Plan to Share IPD: Yes

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

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: January 2024