Phase Ib/II study of certinib in combination with LEE011 in patients with ALK-positive Non-Small Cell Lung Cancer

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 27

Inclusion Criteria

•Male or female aged = 18 years
•Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be ALK-positive as determined by ALK rearrangement in =15% of cells (as measured by FISH using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The analysis may be performed locally.
•Eastern cooperative oncology group (ECOG) performance status = 2.
•Measurable disease as per RECIST v1.1
•Availability of tumor sample:
oFor ALK inhibitor naïve patients:
A representative tumor sample must be submitted. An archival tumor specimen is acceptable
oFor patients after progression on an ALK inhibitor:
A new tumor biopsy is required unless a biopsy performed after progression on the patient’s most recent ALK inhibitor is available for submission
oFor all patients a newly obtained tumor specimen must be submitted if no appropriate archival sample is available. In the event that no sample is available and a new biopsy cannot be obtained, enrollment may be considered after discussion with the sponsor.
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 136
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion Criteria

•For dose escalation part:
oPatients who have received prior treatment with ceritinib cannot be enrolled in the escalation part of the study until a combination drug dose with appropriate ceritinib exposure is determined. Prior therapy with other ALK inhibitors is allowed.
•For Phase II part:
oGroup A: prior therapy with any ALK inhibitor is not permitted.
oGroup B: progression following any ALK inhibitor(s) other than ceritinib is required and the last dose of the ALK inhibitor must be no more than 60 days prior to the first dose of study drug. Prior ceritinib is not permitted.
oGroup C: progression following ceritinib is required and the last dose of ceritinib must be no more than 60 days prior to the first dose of study drug. Patients must have tolerated a dose of ceritinib of 600 mg QD, or greater.
•Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
•Impaired cardiac function or any clinically significant cardiac disease, including any of the following:
oClinically significant heart disease such as CHF requiring treatment (NYH grade = 2), unstable angina pectoris or myocardial infarction within the past 3 months, or left ventricular ejection fraction (LVEF) < 45% or less than the institution lower limit of normal as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
oQT corrected with Fridericia’s (QTcF) >450 ms screening ECG or congenital long QT syndrome or family history of unexpected sudden cardiac death.
oAny other clinically significant heart disease such as unstable arrhythmia, resting bradycardia, left bundle branch block, bifascicular block, or any heart disease that requires the use of a cardiac pacemaker = 3 months prior to starting study drug
•Patients with the following laboratory values during screening and on day 1 of pre-dose:
oHematology
-Absolute neutrophil count (ANC) < 1.5 x 109/L
-Platelet count < 100 x 109/L
-Hemoglobin (Hgb) < 9 g/dL
oBiochemistry
-Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/min
-Total bilirubin > 1.5 x ULN, except for patients with known Gilbert syndrome, who are excluded if total bilirubin is > 3.0 x ULN or direct bilirubin is > 1.5 x ULN
-Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who must have a value = 5 x ULN
-Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who must have a value = 5 x ULN
-Potassium, magnesium or calcium abnormality > CTCAE grade 1 (despite oral supplementation)
-Phosphate abnormality > CTCAE grade 2 (despite oral supplementation)
•Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ceritinib or LEE011 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
•Patients who

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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