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

Non-Small-Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02450903
• Other study ID #: CLDK378A1201
• Status: Completed
• Phase: Phase 2
• Start date: August 21, 2015
• Est. completion date: May 24, 2018

Study information

• Verified date: January 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 24, 2018
• Est. primary completion date: July 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

Drug:
• LDK378
Oral LDK378 750mg once daily

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	Koto ku	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Natori	Miyagi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka Sayama	Osaka
Japan	Novartis Investigative Site	Sakyo Ku	Kyoto

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	6 cycles of 28 days up to 798 days
Secondary	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.	6 cycles of 28 days up to 798 days
Secondary	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	6 cycles of 28 days up to 798 days
Secondary	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	6 cycles of 28 days up to 798 days
Secondary	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.	6 cycles of 28 days up to 798 days
Secondary	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	6 cycles of 28 days up to 798 days