A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma - Full Text View

Purpose

The study will assess the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations.

Condition	Intervention	Phase
BRAF or NRAS Mutant Metastatic Melanoma	Drug: MEK162	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Open-label Study to Assess the Safety and Efficacy of Oral MEK162 in Adults With Locally Advanced and Unresectable or Metastatic Malignant Cutaneous Melanoma, Harboring BRAFV600 or NRAS Mutations

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Overall response rate (ORR) - Efficacy [ Time Frame: every 8 weeks up to end of study ] [ Designated as safety issue: No ]
The primary objective is to estimate the objective responses rate (ORRs) of MEK162 when administered orally as i. 45mg twice-daily, to adult patients with advanced, unresectable cutaneous malignant melanoma, harboring BRAFV600 or NRAS mutations and ii. 60mg twice-daily, to adult patients with advanced, unresectable cutaneous malignant melanoma, harboring BRAFV600 mutations. ORR is defined as the rate of best overall response (CR+PR), determined by RECIST.

Secondary Outcome Measures:

Progression Free SUurvival (PFS) [ Time Frame: every 8 weeks up to end of study ] [ Designated as safety issue: No ]
The key secondary efficacy objective is estimation of progression free survival (PFS) distribution by study arm. PFS is defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause, as per RECIST.
Overall Survival, Duration of response (DoR) and Time to Response [ Time Frame: every 8-12 weeks up to end of study ] [ Designated as safety issue: No ]
These endpoints will allow further analysis of the efficacy of MEK162
Frequency and severity of adverse events and changes in laboratory values [ Time Frame: every 30 days after last dose ] [ Designated as safety issue: Yes ]
To characterize safety and tolerability of MEK162
Change in pharmacodynamics pre- and post-dose [ Time Frame: After 15 days of dosing ] [ Designated as safety issue: No ]
To measure the changes in molecular markers of cell proliferation/survival pre-vs. post-dose tumor tissues and potential correlation with clinical outcomes

Estimated Enrollment:	152
Study Start Date:	March 2011
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1	Drug: MEK162
Experimental: NRAS mutant, 45mg bid 45mg bid	Drug: MEK162
Experimental: BRAFV600 mutant, 60mg bid 60mg bid	Drug: MEK162

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery
BRAF or NRAS mutation in tumor tissue
All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol
Evidence of measurable tumor disease as per RECIST
WHO performance status of 0-2
Adequate organ function and laboratory parameters

Exclusion Criteria:

History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO
Patients with unstable CNS metastasis
Prior treatment with a MEK- inhibitor
Impaired cardiovascular function
HIV, active Hepatitis B, and/or active Hepatitis C infection
Pregnant or nursing (lactating) women
Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320085

Contacts

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

Locations

United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp	Recruiting
Fayetteville, Arkansas, United States, 72703
Contact: Vicki Weaver 479-872-8130 vweaver@hogonc.com
Principal Investigator: Joseph T Beck
United States, Florida
H. Lee Moffitt Cancer Center/University of South Florida Moffitt 5	Recruiting
Tampa, Florida, United States, 33612
Contact: Amber Isley 813-745-3437 amber.isley@moffitt.org
Principal Investigator: Geoffrey Gibney
United States, Massachusetts
Dana Farber Cancer Institute DFCI (4)	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Janice Russell Janice_Russell@dfci.harvard.edu
Principal Investigator: Nageatte Ibrahim
United States, Oregon
Oregon Health & Science University OHSU 2	Recruiting
Portland, Oregon, United States, 97239
Contact: Kirsten Orand 503-346-1183
Principal Investigator: Michael Heinrich
United States, Pennsylvania
St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)	Active, not recruiting
Bethlehem, Pennsylvania, United States
United States, South Carolina
Cancer Centers of the Carolinas CCC Faris	Completed
Greenville, South Carolina, United States, 29605
Canada, Alberta
Novartis Investigative Site	Withdrawn
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Novartis Investigative Site	Withdrawn
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Novartis Investigative Site	Withdrawn
Montreal, Quebec, Canada, H3T 1E3
Germany
Novartis Investigative Site	Recruiting
Essen, Germany, 45147
Novartis Investigative Site	Recruiting
Gera, Germany, 07548
Novartis Investigative Site	Recruiting
Kiel, Germany, 24105
Novartis Investigative Site	Recruiting
Muenchen, Germany, 80336
Italy
Novartis Investigative Site	Recruiting
Genova, GE, Italy, 16132
Novartis Investigative Site	Withdrawn
Milano, MI, Italy, 20141
Novartis Investigative Site	Recruiting
Napoli, Italy, 80131
Netherlands
Novartis Investigative Site	Completed
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site	Recruiting
Maastricht, Netherlands, 5800
Novartis Investigative Site	Active, not recruiting
Nijmegen, Netherlands, 6525 GA
Switzerland
Novartis Investigative Site	Completed
Chur, Switzerland, 7000
Novartis Investigative Site	Active, not recruiting
Zürich, Switzerland, 8091

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. doi: 10.1016/S1470-2045(13)70024-X. Epub 2013 Feb 13.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01320085 History of Changes
Other Study ID Numbers:	CMEK162X2201, 2010-023412-13
Study First Received:	March 14, 2011
Last Updated:	January 24, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Metastatic melanoma,
BRAF-mutant,
NRAS-mutant

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on June 17, 2013