A clinical study of oral LDK378 in adult patients with ALK-activated non-small cell lung cancer and who have not been previously treated with crizotinib

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 18.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003474-36-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-11-01
• Study Completion: 2018-01-22
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 124

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of stage IIIb or IV NSCLC that carries an ALK rearrangement as per the FDA-approved Vysis ALK break-apart FISH test (Abbott Molecular Inc)
2. Age 18 years or older at the time of informed consent.
3. Patients must have NSCLC that has progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was recieved.
4. Patients must be chemotherapy-naive or have received 1-3 lines of cytotoxic chemotherapy to treat their locally advanced or metastatic NSCLC
5. Patients must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
6. 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

Other protocol defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC
2. Patients with know hypersensitivity to any of the excipients of LDK378
3. 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.
4. History of carcinomatous meningitis.
5. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
6. Clinically significant, uncontrolled heart disease

Other protocol defined exclusion criteria may apply

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the antitumor activity of LDK378, as measured by overall response rate (ORR) to LDK378 by investigator assessment;Primary end point(s): ORR per RECIST v1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator;Timepoint(s) of evaluation of this end point: 6 cycles of 28 days up to 24 weeks;<br> Secondary Objective: To evaluate response related endpoints as assessed by investigator and Blinded Independent Review Committee (BIRC):<br> - Duration of response (DOR)<br> - Disease control rate (DCR)<br> - Time to response (TTR)<br> To assess ORR by BIRC assessment<br> To evaluate the safety profile of LDK378<br> To evaluate progression-free survival (PFS)<br> To evaluate overall survival (OS)<br> To evaluate overall intracranial response rate (OIRR)<br>