- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01801358
A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Paris, France, 75231
- Pfizer Investigative Site
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Essen, Germany, 45147
- Pfizer Investigative Site
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Leiden, Netherlands, 2300 RC
- Pfizer Investigative Site
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Madrid, Spain, 28050
- Pfizer Investigative Site
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London, United Kingdom, SW3 6JJ
- Pfizer Investigative Site
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute Dept. Onc
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New York
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New York, New York, United States, 90033
- Memorial Sloan Kettering Cancer Center Dept of Onc..
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Arm A
AEB071 and MEK162 combined
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Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles)
Other Names:
Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
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EXPERIMENTAL: Arm B
MEK162 alone
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Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle
Time Frame: Cycle 1 (up to 28 days)
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A DLT is defined as an adverse event or abnormal laboratory value as defined in the protocol that is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with AEB071 and MEK162.
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Cycle 1 (up to 28 days)
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Phase II: Progression Free Survival (PFS)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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The time from date of randomization to the date of event defined as the first documented progression or death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination. |
From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
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From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Serious adverse event (SAE) is defined as one of the following:
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From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR)
Time Frame: Cycle 1 (up to 28 days)
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Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. |
Cycle 1 (up to 28 days)
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Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR)
Time Frame: Cycle 1 (up to 28 days)
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Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. Duration of Response (DOR) is not reported, since there were no responses of Complete Response (CR) or Partial Response (PR) at any time during the study. |
Cycle 1 (up to 28 days)
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Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS)
Time Frame: Cycle 1 (up to 28 days)
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Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. |
Cycle 1 (up to 28 days)
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Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR). This is also referred to as 'Objective response rate' in some protocols or publications. Due to an enrollment halt, the Phase II part of the study was not conducted. |
From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Progressive Disease (PD) the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Due to an enrollment halt, the Phase II part of the study was not conducted. |
From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Duration of Response is not reported, due to the enrollment halt, which occurred prior to Phase II of the study. |
From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS)
Time Frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. |
From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
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Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1)
Time Frame: Cycle 1 (Day 1)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 1)
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Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15)
Time Frame: Cycle 1 (Day 15)
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Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling.
On Days 8 and 22 of Cycle 1, trough samples were collected.
Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
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Cycle 1 (Day 15)
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CMEK162X2203
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uveal Melanoma
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedIris Melanoma | Medium/Large Size Posterior Uveal Melanoma | Stage IIA Uveal Melanoma | Stage IIB Uveal Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal MelanomaUnited States
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National Cancer Institute (NCI)ExelisisCompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal Melanoma | Stage III Uveal Melanoma AJCC v7 | Stage IIIA Uveal Melanoma AJCC v7 | Stage IIIB Uveal Melanoma AJCC v7 | Stage IIIC Uveal Melanoma AJCC v7United States, Canada
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Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)TerminatedStage IV Uveal Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedIris Melanoma | Stage IV Uveal Melanoma | Medium/Large Size Posterior Uveal Melanoma | Recurrent Uveal Melanoma | Ocular Melanoma With Extraocular Extension | Small Size Posterior Uveal MelanomaUnited States, Canada
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Alliance for Clinical Trials in OncologyWithdrawnMetastatic Uveal Melanoma | Advanced Uveal Melanoma | Unresectable Uveal Melanoma
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Cutaneous Melanoma AJCC v6 and v7 | Recurrent Melanoma | Stage IIIC Cutaneous Melanoma AJCC v7 | Mucosal Melanoma | Iris Melanoma | Stage IIIA Cutaneous Melanoma AJCC v7 | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage IV Uveal Melanoma AJCC v7 | Medium/Large Size Posterior Uveal Melanoma | Recurrent... and other conditionsUnited States
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National Cancer Institute (NCI)Memorial Sloan Kettering Cancer Center; Institut Curie Paris; Moffitt Cancer...Active, not recruitingMetastatic Uveal Melanoma | Stage IV Uveal Melanoma AJCC v7United States
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National Cancer Institute (NCI)CompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal MelanomaUnited States, France, United Kingdom
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NovartisCompleted
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Novartis PharmaceuticalsCompletedModerate and Severe Plaque PsoriasisUnited States, Argentina, Germany, Belgium, Italy, United Kingdom, Turkey, Guatemala, Australia
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Columbia UniversityCompleted
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NovartisCompletedde Novo Liver TransplantationGermany, Italy, Switzerland
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Novartis PharmaceuticalsCompletedKidney TransplantationUnited States, United Kingdom, Germany, Belgium, Spain, Canada, Sweden