Clinical trial NCT01801358: A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
Official title: A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Uveal Melanoma
Keywords: Melanoma,
melanoma of the eye,
uveal,
MEK162,
AEB071
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2013-02-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: Due to halted enrollment, the Phase II part of the study was not conducted. The Sponsor decided to permanently stop recruitment for the study prior to MTD determination.

Remaining patients on treatment with binimetinib and sotrastaurin who were considered by the Investigator to be benefiting from their treatment could have continued treatment and were to be followed up as per protocol. No patients were ongoing as of the data cut-off date. After the last patient last visit (LPLV) was declared, the study was terminated.

Eligibility 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

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

Primary outcomes:
measure: Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle
timeFrame: Cycle 1 (up to 28 days)
measure: Phase II: Progression Free Survival (PFS)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Secondary outcomes:
measure: Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR)
timeFrame: Cycle 1 (up to 28 days)
measure: Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR)
timeFrame: Cycle 1 (up to 28 days)
measure: Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS)
timeFrame: Cycle 1 (up to 28 days)
measure: Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS)
timeFrame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
measure: Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
measure: Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
measure: Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
measure: Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1)
timeFrame: Cycle 1 (Day 1)
measure: Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
measure: Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
measure: Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15)
timeFrame: Cycle 1 (Day 15)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute Dept. Onc
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Dept of Onc..
state: New York
city: Paris
country: France
facility: Pfizer Investigative Site
city: Essen
country: Germany
facility: Pfizer Investigative Site
city: Leiden
country: Netherlands
facility: Pfizer Investigative Site
city: Madrid
country: Spain
facility: Pfizer Investigative Site
city: London
country: United Kingdom
facility: Pfizer Investigative Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: