Back to results

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

Primary Purpose

Non-Small-Cell Lung Cancer

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

LDK378

About this trial

This is an interventional treatment trial for Non-Small-Cell Lung Cancer focused on measuring Non-Small-Cell Lung Cancer, NSCLC, ALK, LDK378, alectinib, Non-small cell lung carcinoma (NSCLC), lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LDK378 (Ceritinib)

Arm Description

Participants who received LDK378 750mg once daily on a 28 day cycle.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Disease Control Rate (DCR)

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.

Time to Tumor Response (TTR)

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.

Duration of Response (DOR)

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

Progression Free Survival (PFS)

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

Overall Survival (OS)

OS was defined as the time from the start date of study drug to the date of death due to any cause.

Overall Intracranial Response Rate (OIRR)

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

Full Information

NCT ID

NCT02450903

First Posted

May 8, 2015

Last Updated

March 26, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02450903

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

August 21, 2015 (Actual)

Primary Completion Date

July 31, 2017 (Actual)

Study Completion Date

May 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small-Cell Lung Cancer

Keywords

Non-Small-Cell Lung Cancer, NSCLC, ALK, LDK378, alectinib, Non-small cell lung carcinoma (NSCLC), lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LDK378 (Ceritinib)

Arm Type

Experimental

Arm Description

Participants who received LDK378 750mg once daily on a 28 day cycle.

Intervention Type

Drug

Intervention Name(s)

LDK378

Other Intervention Name(s)

Oral LDK378 750mg once daily

Intervention Description

Oral LDK378 750mg once daily

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR) to LDK378 by Investigator Assessment

Description

Time Frame

Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days

Secondary Outcome Measure Information:

Title

Disease Control Rate (DCR)

Description

Time Frame