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

This study has been terminated.
(The trial was terminated for scientific reasons.)
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01801358
First received: February 21, 2013
Last updated: August 29, 2016
Last verified: August 2016
Results First Received: May 12, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Uveal Melanoma
Interventions: Drug: AEB071
Drug: MEK162

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The CMEK162X2203 study began recruitment on 26-Aug-2013 and concluded on 15-May-2015. 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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Participant Flow and Baseline Demographics data represents the Full Analysis Set (FAS), which includes all patients who received at least one full or partial dose of sotrastaurin or binimetinib.

Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason.


Reporting Groups
  Description
Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.


Participant Flow:   Overall Study
    Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS)   Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS)   Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS)
STARTED   6   6   6   6   6   8 
COMPLETED   0   0   0   0   0   0 
NOT COMPLETED   6   6   6   6   6   8 
Adverse Event                0                2                1                0                0                1 
Physician Decision                0                0                1                0                0                0 
Progressive Disease                6                4                4                5                6                5 
Withdrawal by Subject                0                0                0                1                0                2 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline Demographics data represents the Full Analysis Set (FAS), which includes all patients who received at least one full or partial dose of sotrastaurin or binimetinib.

Reporting Groups
  Description
Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Total Total of all reporting groups

Baseline Measures
   Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS)   Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS)   Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS)   Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS)   Total 
Overall Participants Analyzed 
[Units: Participants]
 6   6   6   6   6   8   38 
Age 
[Units: Participants]
             
<=18 years   0   0   0   0   0   0   0 
Between 18 and 65 years   5   5   5   3   4   5   27 
>=65 years   1   1   1   3   2   3   11 
Age 
[Units: Years]
Mean (Standard Deviation)
 48.7  (15.21)   57.0  (10.43)   52.8  (10.82)   59.8  (9.11)   56.8  (10.87)   61.5  (10.65)   56.4  (11.39) 
Gender 
[Units: Participants]
             
Female   3   2   3   2   2   2   14 
Male   3   4   3   4   4   6   24 
Race/Ethnicity, Customized 
[Units: Participants]
             
Hispanic or Latino   1   1   2   1   1   0   6 
Russian   1   0   0   0   0   0   1 
Unknown   2   4   2   1   1   0   10 
Other   2   1   2   4   4   8   21 
Region of Enrollment 
[Units: Participants]
             
Netherlands   0   0   1   1   1   2   5 
United States   1   0   2   2   2   0   7 
United Kingdom   0   1   0   0   1   0   2 
France   2   3   1   1   0   0   7 
Germany   2   1   0   1   1   6   11 
Spain   1   1   2   1   1   0   6 
Baseline WHO Performance Status [1] 
[Units: Participants]
             
0:   3   6   5   5   5   8   32 
1:   3   0   1   1   1   0   6 
[1]

Categories:

  • 0 - Fully active, able to carry on all pre-disease performance without restriction
  • 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  • 2 - Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
  • 3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
  • 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle   [ Time Frame: Cycle 1 (up to 28 days) ]

2.  Primary:   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) ]

3.  Secondary:   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) ]

4.  Secondary:   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) ]

5.  Secondary:   Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR)   [ Time Frame: Cycle 1 (up to 28 days) ]

6.  Secondary:   Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR)   [ Time Frame: Cycle 1 (up to 28 days) ]

7.  Secondary:   Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS)   [ Time Frame: Cycle 1 (up to 28 days) ]

8.  Secondary:   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) ]

9.  Secondary:   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) ]

10.  Secondary:   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) ]

11.  Secondary:   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) ]

12.  Secondary:   Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

13.  Secondary:   Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

14.  Secondary:   Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

15.  Secondary:   Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]

16.  Secondary:   Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]

17.  Secondary:   Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]

18.  Secondary:   Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

19.  Secondary:   Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

20.  Secondary:   Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1)   [ Time Frame: Cycle 1 (Day 1) ]

21.  Secondary:   Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]

22.  Secondary:   Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]

23.  Secondary:   Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15)   [ Time Frame: Cycle 1 (Day 15) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Array BioPharma, Inc.
phone: 303-381-6604
e-mail: clinicaltrials@arraybiopharma.com



Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01801358     History of Changes
Other Study ID Numbers: CMEK162X2203
Study First Received: February 21, 2013
Results First Received: May 12, 2016
Last Updated: August 29, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency