Non-Small Cell Lung Cancer Clinical Trial
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
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
Status | Completed |
Enrollment | 141 |
Est. completion date | March 2016 |
Est. primary completion date | March 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Canada | Novartis Investigative Site | Edmonton | Alberta |
Canada | Novartis Investigative Site | Oshawa | Ontario |
Canada | Novartis Investigative Site | Toronto | Ontario |
France | Novartis Investigative Site | Marseille cedex 20 | |
France | Novartis Investigative Site | Paris | |
Germany | Novartis Investigative Site | Heidelberg | |
Germany | Novartis Investigative Site | Koeln | Nordrhein-Westfalen |
Hong Kong | Novartis Investigative Site | Hong Kong | |
Italy | Novartis Investigative Site | Avellino | AV |
Italy | Novartis Investigative Site | Livorno | LI |
Italy | Novartis Investigative Site | Milano | MI |
Italy | Novartis Investigative Site | Monza | MB |
Italy | Novartis Investigative Site | Parma | PR |
Italy | Novartis Investigative Site | Perugia | PG |
Japan | Novartis Investigative Site | Akashi | Hyogo |
Japan | Novartis Investigative Site | Chuo-ku | Tokyo |
Japan | Novartis Investigative Site | Fukuoka | |
Japan | Novartis Investigative Site | Kashiwa | Chiba |
Japan | Novartis Investigative Site | Koto | Tokyo |
Japan | Novartis Investigative Site | Nagoya | Aichi |
Japan | Novartis Investigative Site | Okayama-city | Okayama |
Japan | Novartis Investigative Site | OsakaSayama | Osaka |
Japan | Novartis Investigative Site | Sunto-gun | Shizuoka |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
Netherlands | Novartis Investigative Site | Amsterdam | |
Netherlands | Novartis Investigative Site | Groningen | |
Netherlands | Novartis Investigative Site | Maastricht | |
Singapore | Novartis Investigative Site | Singapore | |
Spain | Novartis Investigative Site | Barcelona | Catalunya |
Spain | Novartis Investigative Site | La Coruna | Galicia |
Spain | Novartis Investigative Site | Madrid | |
Spain | Novartis Investigative Site | Sevilla | Andalucia |
United Kingdom | Novartis Investigative Site | London | |
United States | Emory University School of Medicine/Winship Cancer Institute Dept of Oncology | Atlanta | Georgia |
United States | University of Colorado Hospital SC | Aurora | Colorado |
United States | Massachusetts General Hospital Mass General | Boston | Massachusetts |
United States | Levine Cancer Institute SC 1 | Charlotte | North Carolina |
United States | University of Chicago Medical Center SC | Chicago | Illinois |
United States | U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office | Dallas | Texas |
United States | City of Hope National Medical Center Dept of Oncology 2 | Duarte | California |
United States | Highlands Oncology Group Dept of Highlands Oncology Grp | Fayetteville | Arkansas |
United States | University of Kansas Cancer Center DeptofUofKansas CancerCenter-2 | Kansas City | Kansas |
United States | University of California at Los Angeles UCLA - Santa Monica 2 | Los Angeles | California |
United States | University of Wisconsin Univ Wisc 2 | Madison | Wisconsin |
United States | Sarah Cannon Research Institute Drug Ship - 4 | Nashville | Tennessee |
United States | Maryland Oncology Hematology, P.A. SC | Rockville | Maryland |
United States | University of California at San Diego, Moores Cancer Ctr SC | San Diego | California |
United States | Seattle Cancer Care Alliance SC-1 | Seattle | Washington |
United States | Stanford University Medical Center Stanford Cancer Center(2) | Stanford | California |
United States | Cancer Center of Kansas Dept of CCK | Wichita | Kansas |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Overall response rate (ORR) to LDK378 by investigator assessment | 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 | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Duration of response (DOR) | 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) | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Disease control rate (DCR) | DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Time to Response (TTR) | TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC | 6 cycles of 28 days up to 24 weeks | No |
Secondary | ORR by BIRC assessment | ORR (CR+PR) per RECIST 1.1 as assessed by BIRC | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Safety profile | Adverse events and laboratory abnormalities | 6 cycles of 28 days up to 24 weeks | Yes |
Secondary | Progression-free survival (PFS) | PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Overall survival (OS) | OS, defined as time from first dose of LDK378 to death due to any cause | 6 cycles of 28 days up to 24 weeks | No |
Secondary | Overall intracranial response rate (OIRR) | OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline | 6 cycles of 28 days up to 24 weeks | No |
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