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
Verified date | March 2019 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
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,
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 |
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