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 will continue until the patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anti-cancer therapy and/or dies. LDK378 may be continued beyond RECIST-defined PD as assessed by the investigator if, in the judgment of the investigator, there is evidence of clinical benefit. In these patients tumor assessment should continue as per the schedule of assessments until treatment with LDK378 is permanently discontinued. Patients who discontinue the study medication in the absence of progression will continue 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:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label 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:

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Overall response rate (ORR) to LDK378 by investigator assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator

Secondary Outcome Measures:

Duration of response (DOR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
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 investigator and BIRC (Blinded Imaging Review Committee)
Disease control rate (DCR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC
Time to Response (TTR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC
ORR by BIRC assessment [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
ORR (CR+PR) per RECIST 1.1 as assessed by BIRC
Safety profile [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: Yes ]
Adverse events and laboratory abnormalities
Progression-free survival (PFS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment
Overall survival (OS) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
OS, defined as time from first dose of LDK378 to death due to any cause
Overall intracranial response rate (OIRR) [ Time Frame: 6 cycles of 28 days up to 24 weeks ] [ Designated as safety issue: No ]
OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline


Enrollment:	141
Study Start Date:	November 2012
Estimated Study Completion Date:	September 2015
Estimated Primary Completion Date:	September 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LDK378 Oral LDK378 750 mg once daily	Drug: LDK378 Other Name: Oral LDK378 750mg once daily

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Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

No publications provided


Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01685060 History of Changes
Other Study ID Numbers:	CLDK378A2201, 2012-003432-24
Study First Received:	September 4, 2012
Last Updated:	October 3, 2014
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Hong Kong: Department of Health Italy: Ministry of Health Japan: Pharmaceuticals and Medical Devices Agency Korea: Food and Drug Administration Netherlands: Medicines Evaluation Board (MEB) Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:


Non-Small Cell Lung Cancer, ALK, LDK378

Additional relevant MeSH terms:


Carcinoma, Non-Small-Cell Lung Lung Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases	Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

ClinicalTrials.gov processed this record on February 27, 2015