Uveal Melanoma
Conditions
Interventions
Product Code: AEB071
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOTRASTAURIN
CAS Number: 425637-18-9
Current Sponsor code: AEB071
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
Novartis Pharma Services
Eligibility
Sex/Gender
All
Inclusion criteria
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 Other inclusion criteria apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
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MEK162 - Treatment with medicines or herbal supplements that are known inhibitors or inducers of CYP3A4/5 and cannot be withdrawn prior to study treatment - Females of child-bearing potential who are unwilling or unable to use highly effective means of contraception - Males who are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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: Estimate the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the AEB071 and MEK162 combination in patients with metastatic uveal melanoma Phase II: Assess the preliminary evidence for anti-tumor activity at the RP2D for AEB071 and MEK162 and at the RP2D for MEK162 alone;Secondary Objective: Phase Ib/II: Further characterize the safety and tolerability of the combination of AEB071 and MEK162, including acute and chronic toxicities Phase Ib: To assess the preliminary anti-tumor activity of the combination of AEB071 and MEK162 To characterize the PK profiles of AEB071 and MEK162, as well as evaluate their active metabolites Phase II: Evaluate the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID of MEK162 alone;Primary end point(s): Phase I: Dose limiting toxicity (DLT) Phase II: Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: Phase I: Up to 28 days of treatment with AEB071 and MEK162 Phase II: From first dose cycle 1, day 1 (C1D1) to time to progression up to 18 months from Last Patient First Visit (LPFV) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Duration of Response (Phase Ib and Phase II) b) Best Overall Response (Phase Ib and Phase II) c) Progession-free survival (Phase Ib) d) Overall survival e) Safety and tolerability of AEB071 and MEK162 (Phase II) f) Blood concentrations of AEB071, MEK162 and their active metabolites (Phase Ib) g) Overall Response Rate (Phase Ib and Phase II);Timepoint(s) of evaluation of this end point: a) From first dose (C1D1) to time to progression up to 18 months from LPFV b) From first dose (C1D1) to time to progression up to 18 months from LPFV c) From first dose (C1D1) to time to progression up to 18 months from LPFV d) From LPFV to death or lost to follow-up up to 18 months from LPFV e) From consent to 30-days post-end-of-treatment f) up to 28 days g) Form first dose (C1D1) to time to progression up to 18 months from LPFV | — |
Countries
France, Germany, Italy, Netherlands, Norway, Spain, United Kingdom
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed