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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
  Purpose

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


Condition Intervention Phase
Uveal Melanoma
Drug: AEB071
Drug: MEK162
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 157
Study Start Date: August 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
AEB071 and MEK162 combined
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 B
MEK162 alone
Drug: MEK162
Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01801358

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Massachusetts
Dana Farber Cancer Institute Dept. Onc Recruiting
Boston, Massachusetts, United States, 02115
Contact: Azra Haider    617-582-7116    AHAIDER1@partners.org   
Principal Investigator: Stephen J. Hodi         
United States, New York
Memorial Sloan Kettering Cancer Center Dept of Onc.. Recruiting
New York, New York, United States, 10021
Contact: Natasha Martin    646-888-4339    martinn@mskcc.org   
Principal Investigator: Gary K. Schwartz         
United States, Pennsylvania
Thomas Jerfferson University Hospital SC Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107-5098
Contact: Linda Sailor    215-955-9980    IDS-Service.Pharmacy@jeffersonhospital.org   
Principal Investigator: Takami Sato         
Australia, New South Wales
Novartis Investigative Site Not yet recruiting
Westmead, New South Wales, Australia, 2145
Canada, Ontario
Novartis Investigative Site Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site Recruiting
Paris, France, 75231
Germany
Novartis Investigative Site Not yet recruiting
Berlin, Germany, 12200
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Contact: Sebastien Bauer, M.D.    +49 (0) 201-723-2014    sebastian.bauer@uk.essen.de   
Italy
Novartis Investigative Site Not yet recruiting
Padova, PD, Italy, 35100
Netherlands
Novartis Investigative Site Recruiting
Leiden, Netherlands, 2300 RC
Norway
Novartis Investigative Site Not yet recruiting
Oslo, Norway, NO-0379
Spain
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, SW3 6JJ
Novartis Investigative Site Not yet recruiting
Wirral, United Kingdom, CH63 3JY
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01801358     History of Changes
Other Study ID Numbers: CMEK162X2203
Study First Received: February 21, 2013
Last Updated: June 9, 2014
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

Keywords provided by Novartis:
Melanoma,
melanoma of the eye,
uveal,
MEK162,
AEB071

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases

ClinicalTrials.gov processed this record on November 23, 2014