Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

Study Overview
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Brief Summary
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This study has two parts, dose escalation and dose expansion. For dose escalation, the primary objective is to estimate the maximum tolerated dose (MTD) of AEB071 in patients with uveal melanoma. For dose expansion, the primary objective is to characterize the safety and tolerability of the MTD of AEB071 in patients with uveal melanoma.

Official Title
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A Phase 1 Study of AEB071, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma

Conditions
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Uveal Melanoma

Intervention / Treatment
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* Drug: AEB071


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Uveal melanoma with biopsy proven metastatic disease Males and females ≥ 18 years of age Consent to biopsy of tumor Measurable disease according to RECIST version 1.1 WHO performance status of ≤ 1 Exclusion Criteria: Patients with abnormal laboratory values as defined by the protocol Patients who are receiving treatment with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to study entry Patients with impaired cardiac function or clinically significant cardiac diseases as defined by the protocol Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma Patients with impairment of gastrointestinal function or disease Patients with severe systemic infections Patients who are known to be HIV positive and/or have active hepatitis B or C infection Time since last therapy for treatment of underlying malignancy: Cytotoxic chemotherapy: ≤ duration of the most recent cycle of the previous regimen (a minimum of 2 weeks for all) Nitrosurea: ≤ 6 weeks Biologic therapy: ≤ 4 weeks ≤ 5 x PK half-life of a small molecule therapeutic not otherwise defined above Patients having undergone major surgery less than 4 weeks prior to enrollment or have not fully recovered from prior surgery Women of child-bearing potential unless they are using highly effective methods of contraception during the dosing and for at least 36 hours after last dose. Highly effective contraception as defined in the protocol. Patients with primary central nervous system tumors or brain metastases. Pregnant or nursing (lactating) women. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AEB071<br> | Drug: AEB071<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation |  | cycle 1 (28 days) | 
| Number of participants reporting serious adverse events and adverse events - Dose Expansion |  | Baseline, every 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1 |  | Baseline, 12 months | 
| Progression free survival and time to progression using RECIST version 1.1 |  | Baseline, 12 months | 
| Number of patients reporting serious adverse events and adverse events |  | Baseline, 12 months | 
| AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA |  | First 7 months of treatment period | 
| Gα genotype in tumor specimens |  | Baseline, 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveal melanoma, phase 1, AEB071, Metastatic