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Completed

NCT Number: NCT01685060

LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib

A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined progressive disease (PD) as assessed by the investigator if, in the judgment of the investigator, there was evidence of clinical benefit. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Edmonton, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion critieria:

  • Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
  • Age 18 years or older at the time of informed consent.
  • Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
  • Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
  • Patients must have a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

Exclusion criteria

  • Patients with known hypersensitivity to any of the excipients of LDK378.
  • Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
  • History of carcinomatous meningitis.
  • Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
  • Clinically significant, uncontrolled heart disease
  • Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.

Treatment and study plan

LDK378

Drug

Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).

Other names: Ceritinib

Primary outcomes

  1. Overall Response Rate (ORR) to LDK378 Per Investigator Assessment

    Time frame: 6 cycles of 28 days up to 24 weeks

    ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Secondary outcomes

  1. ORR Per Blinded Independent Review Committee (BIRC) Assessment

    Time frame: 6 cycles of 28 days up to 24 weeks

    ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  2. Duration of Response (DOR) by Investigator

    Time frame: 6 cycles of 28 days up to 24 weeks

    DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  3. Duration of Response (DOR) by BIRC

    Time frame: 6 cycles of 28 days up to 24 weeks

    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  4. Disease Control Rate (DCR)

    Time frame: 6 cycles of 28 days up to 24 weeks

    DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.

  5. Time to Response (TTR) Per Investigator

    Time frame: 6 cycles of 28 days up to 24 weeks

    TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.

  6. Time to Response (TTR) Per BIRC

    Time frame: 6 cycles of 28 days up to 24 weeks

    TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.

  7. Progression-free Survival (PFS) Per Investigator

    Time frame: 6 cycles of 28 days up to 24 weeks

    PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.

  8. Progression-free Survival (PFS) Per BIRC

    Time frame: 6 cycles of 28 days up to 24 weeks

    PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.

  9. Overall Intracranial Response Rate (OIRR) Per Investigator

    Time frame: 6 cycles of 28 days up to 24 weeks

    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.

  10. Overall Intracranial Response Rate (OIRR) Per BIRC

    Time frame: 6 cycles of 28 days up to 24 weeks

    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.

  11. Overall Survival (OS)

    Time frame: 6 cycles of 28 days up to 24 weeks

    OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib

Important dates

Study start
2012
Primary completion
2016
Study completion
2016
First posted
Sep 13, 2012
Registry last updated
Jun 19, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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