LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.
A Phase II, Multi-center, Open-label, Single-Arm Study to Evaluate the Efficacy and Safety of Oral LDK378 Treatment for Patients With ALK-Positive Non-Small Cell Lung Cancer Previously Treated With Alectinib
1 other identifier
interventional
20
1 country
9
Brief Summary
This was a single-arm, open-label, multicenter, phase II study to evaluate the efficacy and safety of the ALK inhibitor LDK378 when used as single agent in patients with ALK-rearranged stage IIIB or IV NSCLC previously treated with alectinib. Treatment with LDK378 750 mg qd continued until the patient experienced disease progression as determined by the investigator according to RECIST 1.1, unacceptable toxicity that precluded further treatment, pregnancy, start of a new anticancer therapy, discontinued treatment at the discretion of the patient or investigator, lost to follow-up, death, or study was terminated by Sponsor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Aug 2015
Typical duration for phase_2
9 active sites
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
May 8, 2015
CompletedFirst Posted
Study publicly available on registry
May 21, 2015
CompletedStudy Start
First participant enrolled
August 21, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 24, 2018
CompletedResults Posted
Study results publicly available
December 24, 2020
CompletedMarch 30, 2021
January 1, 2021
1.9 years
May 8, 2015
May 22, 2019
March 26, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) to LDK378 by Investigator Assessment
ORR, defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 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.
Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days
Secondary Outcomes (6)
Disease Control Rate (DCR)
6 cycles of 28 days up to 798 days
Time to Tumor Response (TTR)
6 cycles of 28 days up to 798 days
Duration of Response (DOR)
6 cycles of 28 days up to 798 days
Progression Free Survival (PFS)
6 cycles of 28 days up to 798 days
Overall Survival (OS)
6 cycles of 28 days up to 798 days
- +1 more secondary outcomes
Study Arms (1)
LDK378 (Ceritinib)
EXPERIMENTALParticipants who received LDK378 750mg once daily on a 28 day cycle.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of Stage IIIb or IV NSCLC that carries an ALK rearrangement as determined locally by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test.
- Patients must have NSCLC that has progressed at study enrollment.
- Patients must have received previous treatment with alectinib for treatment of locally advanced or metastatic NSCLC. Prior therapy with crizotinib as ALK inhibitor therapy in addition to alectinib is allowed. Alectinib doesn't need to be the last therapy prior to study enrollment. No particular sequence of prior alectinib and crizotinib is required for enrollment.
- Patients must be chemotherapy-naïve or have received only one line of prior cytotoxic chemotherapy.
- Age 18 years or older at the time of informed consent.
You may not qualify if:
- Patients with known hypersensitivity to any of the excipients of LDK378.
- Prior therapy with other ALK inhibitor investigational agents except crizotinib and alectinib.
- Prior systemic anti-cancer (including investigational) therapy aside from alectinib, crizotinib and one regimen of previous cytotoxic chemotherapy for locally advanced or metastatic NSCLC.
- 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.
- Patient with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
- Patients with history of carcinomatous meningitis.
- Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
- Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Novartis Investigative Site
Nagoya, Aichi-ken, 464 8681, Japan
Novartis Investigative Site
Kashiwa, Chiba, 277 8577, Japan
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395, Japan
Novartis Investigative Site
Sakyo Ku, Kyoto, 606 8507, Japan
Novartis Investigative Site
Natori-shi, Miyagi, 981-1293, Japan
Novartis Investigative Site
Okayama, Okayama-ken, 700-8558, Japan
Novartis Investigative Site
Ōsaka-sayama, Osaka, 589 8511, Japan
Novartis Investigative Site
Chuo Ku, Tokyo, 104 0045, Japan
Novartis Investigative Site
Koto Ku, Tokyo, 135 8550, Japan
Related Publications (1)
Hida T, Seto T, Horinouchi H, Maemondo M, Takeda M, Hotta K, Hirai F, Kim YH, Matsumoto S, Ito M, Ayukawa K, Tokushige K, Yonemura M, Mitsudomi T, Nishio M. Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9. Cancer Sci. 2018 Sep;109(9):2863-2872. doi: 10.1111/cas.13721. Epub 2018 Jul 25.
PMID: 29959809DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 8, 2015
First Posted
May 21, 2015
Study Start
August 21, 2015
Primary Completion
July 31, 2017
Study Completion
May 24, 2018
Last Updated
March 30, 2021
Results First Posted
December 24, 2020
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will share
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