NCT02040870

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
103

participants targeted

Target at P50-P75 for phase_1 nonsmall-cell-lung-cancer

Timeline
Completed

Started Mar 2014

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 17, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 20, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

March 7, 2014

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 27, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 27, 2017

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

January 17, 2019

Completed
Last Updated

February 20, 2019

Status Verified

January 1, 2019

Enrollment Period

3.4 years

First QC Date

January 17, 2014

Results QC Date

July 24, 2018

Last Update Submit

January 30, 2019

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell lung CancerNSCLCALKLDK378ALK-rearrangedALK-positiveadvanced non-small cell lung cancer

Outcome Measures

Primary Outcomes (5)

  • 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

    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))

  • 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.

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

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

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

    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)

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

    Tmax is the time to reach maximum plasma concentration.

    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)

  • 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

    up to 41 months

Secondary Outcomes (13)

  • Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment

    40 months

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

    40 months

  • Duration of Response (DOR) Per Investigator Assessment

    40 months

  • Disease Control Rate (DCR) Per Investigator Assessment

    40 months

  • Time to Response (TTR) Per Investigator Assessment

    40 months

  • +8 more secondary outcomes

Study Arms (1)

LDK378

EXPERIMENTAL

daily dosing, 28-day cycle patients

Drug: LDK378

Interventions

LDK378DRUG

750 mg once daily

LDK378

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Chongqing, Chongqing Municipality, 400037, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 51000, China

Location

Novartis Investigative Site

Changchun, Jilin, 130012, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200032, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200433, China

Location

Novartis Investigative Site

Xi’an, Shanxi, 710038, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100021, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Beijing, 100039, China

Location

Novartis Investigative Site

Chongqing, 400038, China

Location

Novartis Investigative Site

Guang Dong Province, 510120, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
novartis.email@novartis.com
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2014

First Posted

January 20, 2014

Study Start

March 7, 2014

Primary Completion

July 27, 2017

Study Completion

July 27, 2017

Last Updated

February 20, 2019

Results First Posted

January 17, 2019

Record last verified: 2019-01

Locations

CN(15)