A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma



Status:Terminated
Conditions:Skin Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:August 2013
End Date:May 2015

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A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

A phase Ib dose-escalation study of the AEB071 and MEK162 combination in adult patients with
confirmed metastatic uveal melanoma. Cohorts of 3-6 patients will be assessed for dose
limiting toxicities (DLTs) during Cycle 1 until the maximum tolerated dose (MTD) of the
combination therapy is determined. The MTD or Phase 2 Recommended Dose (P2RD) will be used
in a Phase II part of the study, which will enrol 55 patients each into two randomized
groups: the combination therapy or MEK162 alone. The Phase II part will continue until proof
of concept is established. Patients will continue treatment as long as clinical benefit is
seen and no limiting adverse toxicity is observed


Inclusion Criteria:

- Written informed consent

- Male and female patients aged 18 years or older

- A history of uveal (ocular) melanoma with biopsy-confirmed metastatic disease

- Consent to providing 3 tumor biopsy samples throughout the course of the study

- Presence of measurable disease

- A WHO performance status of less than or equal to 1

Exclusion Criteria:

- Presence of CNS lesions (stable lesions may be acceptable)

- Previous or concurrent malignancy, other than basal cell or squamous cell carcinoma
of the skin: in situ carcinoma of the cervix, without evidence of recurrence for at
least 3 years; a primary malignancy completely resected and no evidence of recurrence
for at least 3 years

- Adverse event from prior chemotherapy, radiotherapy or surgery that has not recovered
to CTCAE v4.03 Grade 1 or less, except for alopecia/sensory peripheral neuropathy,
which must be less than Grade 2

- History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO

- Impaired cardiac function or clinically significant cardiac disease

- Impaired GI function or disease that could interfere with the absorption of AEB071
and/or MEK162

- Treatment with medicines or herbal supplements that are known inhibitors or inducers
of CYP3A4/5 and cannot be withdrawn prior to study treatment

- Females of child-bearing potential who are unwilling or unable to use highly
effective means of contraception

- Males who are unwilling or unable to use a condom during sexual intercourse

- Prior exposure to a MEK or PKC inhibitor Other inclusion/exclusion criteria apply
We found this trial at
3
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Paris,
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Boston, Massachusetts 02115
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