A Phase I study of AEB071, an oral protein kinase C inhibitor, in patients with metastatic uveal melanoma.

Patients with metastatic uveal melanoma have a very poor prognosis. There are
currently no approved treatments for this condition.
In melanocytic neoplasm including uveal melanoma, mutations affecting either
one of two genes that encode G protein alpha subunits of heterotrimeric G
protein alpha subunits of heterotrimeric G protein complexes are found in most
tumors (van Raamsdonk). Heterotrimeric G proteins physically associate with G
protein-coupled receptors (GPCRs) that are increasingly recognized as promoting
malignancy in diverse cell types. Therapies that are directed at the signaling
cascade downstream of these G proteins are promising for the treatment of uveal
melanoma.
Uveal melanoma cell lines with Ga subunit mutations are preferentially
sensitive to AEB071.
The starting dose will be 300 mg BID, the most extensively used multiple dose
regimen in prior studies in non-oncology indications; however, higher doses of
AEB071 than those currently being used for immunosuppression may be necessary
for anti-tumor activity.
See for more details paragraph 2 of the protocol.

Estimate the maximum tolerated dose (MTD) of AEB071 (dose escalation) and
characterize the safety and tolerability of the MTD or recommended Phase 2 dose
of AEB071 in patients with metastatic uveal melanoma (dose expansion).

An open-label, multicenter, single-arm, phase I dose escalation (Bayesian) and
expansion study.

treatment with AEB071

Toxicity of AEB071 therapy.
Tumor biopsies.
Radiation exposure, CT scan / MRI. Frequent visits and blood sampling.
An overview of all procedures during the visits are given in Appendix B of the
patient information The side effects can be found in Appendix C of the patient
information It is not certain that participation in the research is of direct
benefit, the data gathered can be useful for the future. The burden on the
patients is as expected for a phase I trial.