LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib - Full Text View

Purpose

A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be 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. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. 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

Condition	Intervention	Phase
Non-Small Cell Lung Cancer	Drug: LDK378	Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Crizotinib Ceritinib

U.S. FDA Resources

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:

Overall Response Rate (ORR) to LDK378 Per Investigator Assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by 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 1. 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:

ORR Per Blinded Independent Review Committee (BIRC) Assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Duration of Response (DOR) by Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Duration of Response (DOR) by BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Disease Control Rate (DCR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by 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 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.
Time to Response (TTR) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.
Time to Response (TTR) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.
Progression-free Survival (PFS) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
Progression-free Survival (PFS) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
Overall Intracranial Response Rate (OIRR) Per Investigator [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
Overall Intracranial Response Rate (OIRR) Per BIRC [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
Overall Survival (OS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ]
OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.


Enrollment:	140
Actual Study Start Date:	November 26, 2012
Study Completion Date:	March 29, 2016
Primary Completion Date:	March 29, 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LDK378 Patients treated with ceritinib/LDK378 750 mg once-daily, fasted	Drug: LDK378 Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules). Other Name: Ceritinib

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion critieria:

Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
Age 18 years or older at the time of informed consent.
Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
Patients must have 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 will not be allowed to participate in the study.

Exclusion criteria:

Patients with known hypersensitivity to any of the excipients of LDK378.
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.
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
Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685060

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01685060 History of Changes
Other Study ID Numbers:	CLDK378A2201 2012-003432-24 ( EudraCT Number )
Study First Received:	September 4, 2012
Results First Received:	March 27, 2017
Last Updated:	May 25, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):


Non-Small Cell Lung Cancer NSCLC ALK LDK378 Ceritinib

Additional relevant MeSH terms:


Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases	Carcinoma, Bronchogenic Bronchial Neoplasms Crizotinib Ceritinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

ClinicalTrials.gov processed this record on July 21, 2017