LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01685138
• Other study ID #: CLDK378A2203
• Secondary ID: 2012-003474-36
• Status: Completed
• Phase: Phase 2
• Start date: December 20, 2012
• Est. completion date: January 22, 2018

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was continued beyond RECIST defined progressive disease (PD) as assessed by the investigator, if in the judgment of the investigator, there was evidence of clinical benefit. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: January 22, 2018
• Est. primary completion date: January 22, 2018
• 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 carried an ALK rearrangement, as per the FDA-approved Vysis ALK break-apart FISH assay (Abbott Molecular Inc.)

• Age 18 years or older at the time of informed consent.

• Patients must have NSCLC that had progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was received

• Patients must have been chemotherapy-naive or had received 1-3 lines of cytotoxic chemotherapy to treat their locally advanced or metastatic NSCLC

• Patients must have had a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.

• Patients must have recovered from all toxicities related to prior anticancer therapies to grade = 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who were not allowed to participate in the study.

Key Exclusion criteria:

• Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC

• Patients with known hypersensitivity to any of the excipients of LDK378.

• Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LDK378
LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Franston	Victoria
Australia	Novartis Investigative Site	St Leonards	New South Wales
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Saint Herblain cedex
Hong Kong	Novartis Investigative Site	Hong Kong
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Akashi	Hyogo
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	Sayama	Osaka
Japan	Novartis Investigative Site	Sunto Gun	Shizuoka
Korea, Republic of	Novartis Investigative Site	Seoul	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
New Zealand	Novartis Investigative Site	Auckland
Norway	Novartis Investigative Site	Oslo
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	St-Petersburg
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Sweden	Novartis Investigative Site	Stockholm
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Songkla	Hat Yai
United Kingdom	Novartis Investigative Site	Colchester
United Kingdom	Novartis Investigative Site	London
United States	Massachusetts General Hospital Mass Gen 5	Boston	Massachusetts
United States	U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office	Dallas	Texas
United States	Sarah Cannon Research Institute Drug Ship - 4	Nashville	Tennessee
United States	Washington University School of Medicine Washington University (16)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Norway,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) by Investigator Assessment	ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	ORR by Blinded Independent Review Committee (BIRC)	ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by BIRC. 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Duration of Response (DOR) as Per Investigator	DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by investigator assessment 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Duration of Response (DOR) as Per BIRC	DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC assessment 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Disease Control Rate (DCR) as Per Investigator and BIRC	DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, 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 that would qualify for PD. PD: At least a 20% increase in the sum of diameter of all measured target lesions, 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 5mm.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Time to Response (TTR) as Per Investigator	TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug
Secondary	Time to Response (TTR) as Per BIRC	TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. 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.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Overall Intracranial Response Rate (OIRR) as Per Investigator	OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by investigator.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Overall Intracranial Response Rate (OIRR) as Per BIRC	OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by BIRC.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Progression-free Survival (PFS) Per Investigator and BIRC	PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.	every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years
Secondary	Overall Survival (OS)	OS, defined as time from first dose of LDK378 to death due to any cause	Time from the date of first dose of LDK378 to the date of death due to any cause up to 5 years