LDK378: A Phase I open-label, dose escalation study of LDK378

LDK378: A Phase I open-label, dose escalation study of LDK378 in pediatric patients with malignancies that have a genetic alteration in anaplastic lymphoma kinase (ALK)

Diseases

Patients must be diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Tumor must carry a genetic alteration of ALK, such as a mutation, translocation, or amplification. Testing for ALK status can be done as part of the protocol screening process.

Description

LDK378 is an orally available ALK inhibitor, approximately 20-fold more potent than crizotinib, and is more selective for ALK. It is anticipated the LDK378 may be more active than crizotinib in ALK-driven diseases, and may also be active in the setting of crizotinib-resistant disease. LDK378 will be administered once daily by mouth, NG tube, or G tube on an empty stomach.

Eligibility Criteria

• Patients must be between 12 months and 17 years of age.
• Patients with symptomatic CNS metastases must be neurologically stable and not requiring increasing doses of steroids or local CNS-directed therapy to control CNS disease.
• Must not have clinically significant, uncontrolled heart disease or prolonged QTc interval.
• Presence of any toxicities due to prior cancer therapy must be mild and tolerable.
• Must have adequate organ function as evidenced by laboratory criteria.
• Cannot have impairment of gastrointestinal function or GI disease that may significantly alter the absorption of LDK378 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• No evidence of active viral hepatitis or a known diagnosis of HIV infection (testing not required).
• Must not require therapy with any medications that are strong inhibitors or inducers of CYP3A4/5, substrates of CYP3A4/5 or CYP2C9 with narrow therapeutic indices, or medications known to prolong the QT interval or induce Torsades de Pointes.

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