Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01801358
First received: February 21, 2013
Last updated: June 9, 2014
Last verified: June 2014

February 21, 2013
June 9, 2014
August 2013
August 2015   (final data collection date for primary outcome measure)
  • Phase I: dose limiting toxicity (DLT) [ Time Frame: Up to 28 days of treatment with AEB071 and MEK162 ] [ Designated as safety issue: Yes ]
    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 AEB071and MEK162.
  • Phase II: Progression-Free Survival [ Time Frame: From first dose cycle 1, day 1 (C1D1) to time to progression up to 18 months from Last Patient First Visit (LPFV) ] [ Designated as safety issue: No ]
    The time from date of randomization to the date of event defined as the first documented progression or death due to any cause.
Same as current
Complete list of historical versions of study NCT01801358 on ClinicalTrials.gov Archive Site
  • Duration of Response (Phase Ib and Phase II) [ Time Frame: From first dose (C1D1) to time to progression up to 18 months from LPFV ] [ Designated as safety issue: No ]
    Duration from best response to confirmed disease progression
  • Best Overall Response (Phase Ib and Phase II) [ Time Frame: From first dose (C1D1) to time to progression up to 18 months from LPFV ] [ Designated as safety issue: No ]
    Best response recorded from the start of treatment until disease progression/recurrence (response is SD, PR or CR)
  • Progression-free survival (Phase Ib) [ Time Frame: From first dose (C1D1) to time to progression up to 18 months from LPFV ] [ Designated as safety issue: No ]
    The time from date of randomization to the date of event defined as the first documented progression or death due to any cause.
  • Overall survival [ Time Frame: From Last Patient First Visit (LPFV) to death or lost to follow-up up to 18 months from LPFV ] [ Designated as safety issue: No ]
    The duration of survival from LPFV until confirmed death due to any cause, whether on treatment or not
  • Safety and tolerability of AEB071 and MEK162 (Phase II) [ Time Frame: From consent to 30-days post-end-of-treatment ] [ Designated as safety issue: Yes ]
    Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs), as well as changes in laboratory values and electrocardiograms, dose interruptions, reductions and dose intensity
  • Blood concentrations of AEB071, MEK162 and their active metabolites (Phase Ib) [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
    Determine blood concentrations and fit to standard PK parameters
  • Overall Response Rate (Phase Ib and Phase II) [ Time Frame: From first does (C1D1) to time to progression up to 18 months from LPFV ] [ Designated as safety issue: No ]
    Proportion of patients with a best overall response rate of CR or PR
  • Phase Ib: Disease control rate (DCR) [ Time Frame: From first dose cycle 1 day 1 (C1D1) to time to progression up to 24 months ] [ Designated as safety issue: No ]
    Disease status for all patients according to RECIST 1.1. DCR is defined as all patients that have stable disease (SD), partial response (PR) or complete response (CR). cycle = 28 days
  • Phase II: Disease control rate (DCR) [ Time Frame: at 4 months of treatment ] [ Designated as safety issue: No ]
    Disease status for all patients according to RECIST 1.1. DCR is defined as all patients that have stable disease (SD), PR or CR at 4 months of treatment
  • Duration of Response [ Time Frame: From first dose (C1D1) to time to progression up to 24 months ] [ Designated as safety issue: No ]
    Duration from best response to confirmed disease progression
  • Best Overall Response [ Time Frame: From first dose (C1D1) to time to progression up to 24 months ] [ Designated as safety issue: No ]
    Maximum response at any time during treatment (response is SD, PR or CR)
  • Progression free survival [ Time Frame: From first dose (C1D1) to time to progression up to 24 months ] [ Designated as safety issue: No ]
    Duration of treatment from Cycle 1 Day 1 to confirmed disease progression or withdrawal
  • Overall survival [ Time Frame: From C1D1 to death or lost to follow-up up to 24 months ] [ Designated as safety issue: No ]
    The duration of survival from first treatment (C1D1) until confirmed death due to any cause, whether on treatment or not
  • Safety and tolerability of AEB071 and MEK162 [ Time Frame: From consent to 30-days post-end-of-treatment ] [ Designated as safety issue: Yes ]
    Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs), as well as changes in laboratory values and electrocardiograms, dose interruptions, reductions and dose intensity
  • Blood concentrations of AEB071, MEK162 and their active metabolites (Phase Ib) [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
    Determine blood concentrations and fit to standard PK parameters
Not Provided
Not Provided
 
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

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

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Uveal Melanoma
  • Drug: AEB071
    Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles)
    Other Name: Sotrastaurin
  • Drug: MEK162
    Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
  • Experimental: Arm A
    AEB071 and MEK162 combined
    Interventions:
    • Drug: AEB071
    • Drug: MEK162
  • Experimental: Arm B
    MEK162 alone
    Intervention: Drug: MEK162
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
157
August 2015
August 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Australia,   Canada,   France,   Germany,   Italy,   Netherlands,   Norway,   Spain,   United Kingdom
 
NCT01801358
CMEK162X2203
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP