A phase I, multicenter, open-label dose escalation study of LDK378, administered orally in adult patients with tumors characterized by genetic abnormalities in anaplastic lymphoma kinase(ALK))
Trial Description
This study assessed the safety and efficacy of LDK378 in adult patients with genetic
abnormalities in anaplastic lymphoma kinase (ALK).
Eligibility Requirements
Inclusion Criteria:
- ECOG Performance Status of ≤ 2 and life expectancy of ≥ 12 weeks.
- Diagnosed with a locally advanced or metastatic malignancy that has progressed
despite standard therapy, or for which no effective standard therapy exists. Only
patients with tumors characterized by genetic abnormalities in ALK were enrolled.
- For NSCLC, an ALK translocation must be detected by FISH in ≥ 15% of tumor cells.
- In patients with diseases other than NSCLC, ALK translocation is not required and
overexpression of ALK protein may be considered indicative of a genetic abnormality
in ALK.
- Patients with measurable or non-measurable disease as determined by modified RECIST
version 1.0 in dose-escalation phase, and patients with at least one measurable
lesion as determined by RECIST 1.0 in expansion phase.
Exclusion Criteria:
- Patients with symptomatic central nervous system (CNS) metastases who were
neurologically unstable or required increasing doses of steroids to control their
CNS disease were excluded.
- Patients with a prior or current history of a second malignancy, impaired GI
function, history of pancreatitis or increased amylase or lipase, known diagnosis of
HIV, and clinically significant cardiac disease were excluded.
- Patients treated with chemotherapy or biologic therapy or other investigational
agent < 2 weeks prior to starting study drug for compounds with a half-life ≤ 3
days, and < 4 weeks prior to starting study drug for compounds with a prolonged
half-life were excluded.
- Further, patients treated with medications that were known to be strong inhibitors
or inducers of CYP3A4/5 that could not be discontinued at least a week prior to
start of treatment with LDK378 and for the duration of the study were also excluded.
Other protocol-defined inclusion/exclusion criteria may apply