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Non-Small Cell Lung CancerPhase 2NCT01685138

LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

A Phase 2 study testing LDK378 in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 51 sites in 18 countries.

Completed

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

Official record
Search all trials

Trial summary

A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or… 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
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
51 sitesin 18 countries
Study dates
20 Dec 2012to 22 Jan 2018
Phase
Phase 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 stage IIIB or IV NSCLC that carried an ALK rearrangement, as per the FDA-approved Vysis ALK break-apart FISH assay (Abbott Molecular Inc.)
  • Age 18 years or older at the time of informed consent.
  • Patients must have NSCLC that had progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was received
  • Patients must have been chemotherapy-naive or had received 1-3 lines of cytotoxic chemotherapy to treat their locally advanced or metastatic NSCLC
  • Patients must have had 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 were not allowed to participate in the study.

Who cannot join

  • Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC
  • Patients with known hypersensitivity to any of the excipients of LDK378.
  • Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had 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

51 sites in 18 countries.

51 sites in 18 countries

Japan8 sites

  • Novartis Investigative Site

    Akashi, Hyōgo, 673-8558

  • Novartis Investigative Site

    Chuo-ku, Tokyo, 104-0045

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 811-1395

  • Novartis Investigative Site

    Kashiwa, Chiba, 277 8577

  • Novartis Investigative Site

    Koto Ku, Tokyo, 135 8550

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 464 8681

  • Novartis Investigative Site

    Sayama, Osaka, 589 8511

  • Novartis Investigative Site

    Sunto Gun, Shizuoka, 411 8777

Other trials in Japan

Italy5 sites

  • Novartis Investigative Site

    Avellino, AV, 83100

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Milan, MI, 20141

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Spain5 sites

  • Novartis Investigative Site

    Badalona, Catalonia, 08916

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Madrid, 28046

  • Novartis Investigative Site

    Madrid, 28050

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

Other trials in Spain

United States4 sites

  • Massachusetts General Hospital Mass Gen 5

    Boston, Massachusetts, 02114

  • U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office

    Dallas, Texas, 75390

  • Sarah Cannon Research Institute Drug Ship - 4

    Nashville, Tennessee, 37203

  • Washington University School of Medicine Washington University (16)

    St Louis, Missouri, 63110

Other trials in United States

South Korea4 sites

  • Novartis Investigative Site

    Seoul, Gyeonggi-do, 03080

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, Korea, 06351

  • Novartis Investigative Site

    Seoul, 03722

Other trials in South Korea

Taiwan4 sites

  • Novartis Investigative Site

    Taichung, 407

  • Novartis Investigative Site

    Tainan, Taiwan ROC, 70403

  • Novartis Investigative Site

    Taipei, Taiwan, ROC, 11217

  • Novartis Investigative Site

    Taipei, 10002

Other trials in Taiwan

Thailand4 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Bangkok, 10400

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Songkhla, Hat Yai, 90110

Other trials in Thailand

Russia3 sites

  • Novartis Investigative Site

    Chelyabinsk, 454087

  • Novartis Investigative Site

    Moscow, 115478

  • Novartis Investigative Site

    Saint Petersburg, 197022

Other trials in Russia

Australia2 sites

  • Novartis Investigative Site

    Franston, Victoria, 3199

  • Novartis Investigative Site

    St Leonards, New South Wales, 2065

Other trials in Australia

Belgium2 sites

  • Novartis Investigative Site

    Genk, 3600

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Canada2 sites

  • Novartis Investigative Site

    Saskatoon, Saskatchewan, S7N 4H4

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

United Kingdom2 sites

  • Novartis Investigative Site

    Colchester, CO3 3NB

  • Novartis Investigative Site

    London, SE1 9RT

Other trials in United Kingdom

France1 site

  • Novartis Investigative Site

    Saint-Herblain, 44805

Other trials in France

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

New Zealand1 site

  • Novartis Investigative Site

    Auckland, 1142

Other trials in New Zealand

Norway1 site

  • Novartis Investigative Site

    Oslo, NO-0424

Other trials in Norway

Singapore1 site

  • Novartis Investigative Site

    Singapore, 169610

Other trials in Singapore

Sweden1 site

  • Novartis Investigative Site

    Stockholm, SE 171 76

Other trials in Sweden

About this study

Official title: A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was 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. 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. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).

Being tested
LDK378
Keywords
Non-Small Cell Lung Cancer, Non small cell lung carcinoma, NSCLC, ALK, LDK378, Ceritinib, crizotinib naïve adult patients, ALK-activated non-small cell lung cancer, treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Adenocarcinoma of Lung

What participants receive

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

  • LDK378Drug

    Also called Ceritinib

    LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally

Study groups in NCT01685138
Study groupRoleWhat they receive
LDK378 (Ceritinib)ExperimentalParticipants on this arm took oral LDK378 750 mg once daily.
Receives: Drug: LDK378

What is being measured

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

  1. Overall Response Rate (ORR) by Investigator Assessment

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

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Secondary outcomes (10)

  1. ORR by Blinded Independent Review Committee (BIRC)

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

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  2. Duration of Response (DOR) as Per Investigator

    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, 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.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  3. Duration of Response (DOR) as Per BIRC

    DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC 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.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  4. Disease Control Rate (DCR) as Per Investigator and BIRC

    DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, 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. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions that would qualify for PD. PD: 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 to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  5. Time to Response (TTR) as Per Investigator

    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. 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.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug

  6. Time to Response (TTR) as Per BIRC

    TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. 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.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  7. Overall Intracranial Response Rate (OIRR) as Per Investigator

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

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  8. Overall Intracranial Response Rate (OIRR) as Per BIRC

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

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  9. Progression-free Survival (PFS) Per Investigator and BIRC

    PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.

    Measured: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

  10. Overall Survival (OS)

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

    Measured: Time from the date of first dose of LDK378 to the date of death due to any cause up to 5 years

Timeline

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

  1. First posted14 Sep 2012 (estimated)
  2. Study start20 Dec 2012
  3. Primary completion22 Jan 2018
  4. Study completion22 Jan 2018

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01685138
Sponsor's protocol ID
CLDK378A2203
Other IDs
2012-003474-36
Status last verified
Mar 2019
First submitted
4 Sep 2012
Last updated
26 Mar 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Nishio M, Felip E, Orlov S, Park K, Yu CJ, Tsai CM, Cobo M, McKeage M, Su WC, Mok T, Scagliotti GV, Spigel DR, Viraswami-Appanna K, Chen Z, Passos VQ, Shaw AT. Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC. J Thorac Oncol. 2020 Apr;15(4):609-617. doi: 10.1016/j.jtho.2019.11.006. Epub 2019 Nov 25.

    PubMed 31778798

  • 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.

    PubMed 27130468

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LDK378 in people with Non-Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 51 sites in 18 countries.

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 6 inclusion and 6 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 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in Japan, Italy, Spain, United States, South Korea and 13 more countries. 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 phase mean?

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 12 Feb 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?

Overall Response Rate (ORR) by Investigator Assessment (time frame: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years). 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 NCT01685138, which also lists 2 linked publications.

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 26 Mar 2019.

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