LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.

March 26, 2021 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study completed as per protocol. 'Switched to commercial drug' implies that after the primary and secondary objectives were achieved, one patient continued the study treatment as they did not meet the progression disease or AE to be discontinued from the treatment. But after the regulatory approval, Novartis decided to close the study, the 1 patient switched to commercially available drug.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 464 8681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Japan, 277 8577
        • Novartis Investigative Site
    • Fukuoka
      • Fukuoka-city, Fukuoka, Japan, 811-1395
        • Novartis Investigative Site
    • Kyoto
      • Sakyo Ku, Kyoto, Japan, 606 8507
        • Novartis Investigative Site
    • Miyagi
      • Natori, Miyagi, Japan, 981-1293
        • Novartis Investigative Site
    • Okayama
      • Okayama-city, Okayama, Japan, 700-8558
        • Novartis Investigative Site
    • Osaka
      • Osaka Sayama, Osaka, Japan, 589 8511
        • Novartis Investigative Site
    • Tokyo
      • Chuo ku, Tokyo, Japan, 104 0045
        • Novartis Investigative Site
      • Koto ku, Tokyo, Japan, 135 8550
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: LDK378 (Ceritinib)
Participants who received LDK378 750mg once daily on a 28 day cycle.
Drug: LDK378
Oral LDK378 750mg once daily
Other Names:
  • Oral LDK378 750mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) to LDK378 by Investigator Assessment
Time Frame: Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: 6 cycles of 28 days up to 798 days
DCR, calculated as the percentage of participants with best overall response of CR, PR, or stable disease (SD) evaluated by investigator 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; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD: 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 5 mm.
6 cycles of 28 days up to 798 days
Time to Tumor Response (TTR)
Time Frame: 6 cycles of 28 days up to 798 days
TTR, calculated as the time from first dose of LDK378 to first documented response (CR or PR) evaluated by investigator per RECIST 1.1 for participants with confirmed PR or CR.
6 cycles of 28 days up to 798 days
Duration of Response (DOR)
Time Frame: 6 cycles of 28 days up to 798 days
DOR, calculated as the time from the date of the first documented response (CR or PR) to the first documented disease progression evaluated by investigator per RECIST 1.1 or death due to any cause
6 cycles of 28 days up to 798 days
Progression Free Survival (PFS)
Time Frame: 6 cycles of 28 days up to 798 days
PFS, calculated as the time from first dose of LDK378 to date of first documented disease progression evaluated by investigator per RECIST 1.1 or date of death due to any cause
6 cycles of 28 days up to 798 days
Overall Survival (OS)
Time Frame: 6 cycles of 28 days up to 798 days
OS was defined as the time from the start date of study drug to the date of death due to any cause.
6 cycles of 28 days up to 798 days
Overall Intracranial Response Rate (OIRR)
Time Frame: 6 cycles of 28 days up to 798 days
OIRR, calculated as the percentage of participants with a best overall confirmed response of CR or PR in the brain assessments for participants having measurable brain metastases at baseline
6 cycles of 28 days up to 798 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 21, 2015

Primary Completion (ACTUAL)

July 31, 2017

Study Completion (ACTUAL)

May 24, 2018

Study Registration Dates

First Submitted

May 8, 2015

First Submitted That Met QC Criteria

May 18, 2015

First Posted (ESTIMATE)

May 21, 2015

Study Record Updates

Last Update Posted (ACTUAL)

March 30, 2021

Last Update Submitted That Met QC Criteria

March 26, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLDK378A1201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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