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Non-Small Cell Lung CancerPhase 1/2NCT02040870

LDK378 in Adult Chinese Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib

A Phase 1/2 study testing LDK378 in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 15 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A single-Arm, open-label, multi-center, phase I/II study in which the pharmacokinetics, safety, tolerability and efficacy of LDK378 will be assessed in adult Chinese patients with locally advanced or metastatic NSCLC harboring a confirmed ALK rearrangement. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
LDK378
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
15 sitesChina
Study dates
7 Mar 2014to 27 Jul 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed diagnosis of NSCLC that carries an ALK rearrangement defined as positive using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria) or positive as assessed by the CFDA approved immunohistochemistry (IHC) test (Ventana Medical Systems, Inc)
  • Age 18 years or older at the time of informed consent.
  • Patients must have stage IIIB or IV NSCLC at the time of study entry and have had progressive disease during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. If treated with chemotherapy, maximum 2 lines are allowed.

Who cannot join

  • 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.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

China15 sites

  • Novartis Investigative Site

    Beijing, Beijing Municipality, 100730

  • Novartis Investigative Site

    Beijing, 100021

  • Novartis Investigative Site

    Beijing, 100036

  • Novartis Investigative Site

    Beijing, 100039

  • Novartis Investigative Site

    Changchun, Jilin, 130012

  • Novartis Investigative Site

    Chengdu, Sichuan, 610041

  • Novartis Investigative Site

    Chongqing, Chongqing Municipality, 400037

  • Novartis Investigative Site

    Chongqing, 400038

  • Novartis Investigative Site

    Guang Dong Province, 510120

  • Novartis Investigative Site

    Guangzhou, Guangdong, 51000

  • Novartis Investigative Site

    Guangzhou, 510060

  • Novartis Investigative Site

    Hangzhou, Zhejiang, 310003

  • Novartis Investigative Site

    Shanghai, Shanghai Municipality, 200032

  • Novartis Investigative Site

    Shanghai, Shanghai Municipality, 200433

  • Novartis Investigative Site

    Xi’an, Shanxi, 710038

Other trials in China

About this study

Official title: A Phase I/II, Multicenter, Open-label, Single-arm Study of LDK378, Administered Orally in Adult Chinese Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib Study Type: Interventional

A single-Arm, open-label, multi-center, phase I/II study in which the pharmacokinetics, safety, tolerability and efficacy of LDK378 will be assessed in adult Chinese patients with locally advanced or metastatic NSCLC harboring a confirmed ALK rearrangement. Patients must have demonstrated progression during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. Approximately 100 patients will be enrolled. For the first 15 patients enrolled in this study, patients will have an additional 5-day PK run-in period before treatment period. The pharmacokinetics profile of LDK378 in Chinese adult patients with ALK-rearranged NSCLC will be evaluated.

Read the detailed description

This is a phase I/II, open-label, multi-center study in which the PK, safety, tolerability and efficacy of LDK378 will be assessed in adult Chinese patients with locally advanced or metastatic NSCLC harboring a confirmed ALK rearrangement (positive) as assessed using the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) or positive as assessed by immunohistochemistry (IHC) test (Ventana Medical Systems, Inc) using rabbit monoclonal primary antibody assay (D5F3).

Patients must have demonstrated progression during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy.

Approximately 100 patients with locally advanced or metastatic NSCLC which carry ALK -rearrangement will be enrolled in the study. The first 15 patients to be enrolled in the study will have PK sampling over 120-hour during the 5-day PK run-in period following a single oral dose at 750 mg. After the PK run-in period, the treatment period will start in which LDK378 will be given starting on Cycle 1 Day 1 in a continuous daily oral dosing in 28-day cycles. Separated from these 15 patients, the rest of the enrolled patients will receive LDK378 treatment at 750 mg QD on Cycle 1 Day 1.

Tumor response will be evaluated every 8 weeks (i.e. every 2 cycles) starting from the first day of treatment with LDK378 until the time of RECIST-defined PD by investigator assessment, withdrawal of consent for further follow-up, loss to follow-up or death.

Being tested
LDK378
Keywords
Non-Small Cell lung Cancer, NSCLC, ALK, LDK378, ALK-rearranged, ALK-positive, advanced non-small cell lung cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LDK378Drug

    750 mg once daily

Study groups in NCT02040870
Study groupRoleWhat they receive
LDK378Experimentaldaily dosing, 28-day cycle patients
Receives: Drug: LDK378

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf

    AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time.

    AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.

    AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity

    Measured: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))

  2. Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h

    AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.

    Measured: Cycle 2 Day 1 (after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

  3. Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax

    Cmax is the maximum (peak) concentration of drug in plasma

    Measured: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

  4. Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax

    Tmax is the time to reach maximum plasma concentration.

    Measured: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

  5. Overall Summary of Adverse Events (AEs) - Per Occurence

    Safety and tolerability of LDK378 at 750 mg once daily dose in Chinese adult patients with ALK-rearranged locally advanced or metastatic NSCLC

    Measured: up to 41 months

Secondary outcomes (13)

  1. Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment

    ORR calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  2. ORR Per RECIST 1.1 Per Blind Independent Review Committee (BIRC) Assessment

    ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  3. Duration of Response (DOR) Per Investigator Assessment

    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  4. Disease Control Rate (DCR) Per Investigator Assessment

    DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD 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.

    Measured: 40 months

  5. Time to Response (TTR) Per Investigator Assessment

    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  6. Overall Intracranial Response Rate (OIRR) Per Investigator Assessment

    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  7. Overall Intracranial Response Rate (OIRR) Per BIRC Assessment

    OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  8. Progression Free Survival (PFS) Per Investigator Assessment

    PFS, defined as time from first dose of LDK378 to progression or death due to any cause.

    Measured: 40 months

  9. Overall Survival (OS)

    OS, defined as time from first dose of LDK378 to death due to any cause.

    Measured: 40 months

  10. Duration of Response (DOR) Per BIRC Assessment

    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  11. Disease Control Rate (DCR) Per BIRC Assessment

    DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD 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.

    Measured: 40 months

  12. Time to Response (TTR) Per BIRC Assessment

    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: 40 months

  13. Progression Free Survival (PFS) Per BIRC Assessment

    PFS, defined as time from first dose of LDK378 to progression or death due to any cause.

    Measured: 40 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2014 (estimated)
  2. Study start7 Mar 2014
  3. Primary completion27 Jul 2017
  4. Study completion27 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02040870
Sponsor's protocol ID
CLDK378A2109
Status last verified
Jan 2019
First submitted
17 Jan 2014
Last updated
20 Feb 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: 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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LDK378 in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 15 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf (time frame: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02040870.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2019.

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