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

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Brief Title

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

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle

Secondary Outcome

 Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE)

Condition

Uveal Melanoma

Intervention

AEB071

Study Arms / Comparison Groups

 Arm A
Description:  AEB071 and MEK162 combined

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

38

Start Date

August 2013

Completion Date

May 2015

Primary Completion Date

May 2015

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Pfizer CT.gov Call Center, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01801358

Organization ID

CMEK162X2203


Responsible Party

Sponsor

Study Sponsor

Array Biopharma, now a wholly owned subsidiary of Pfizer


Study Sponsor

Pfizer CT.gov Call Center, Study Director, Pfizer


Verification Date

September 2020