A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01320085
First received: March 14, 2011
Last updated: January 6, 2014
Last verified: January 2014
  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:


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: 181
Study Start Date: March 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 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
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: NCT01320085

Locations
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Moffitt 5
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana Farber Cancer Institute DFCI (4)
Boston, Massachusetts, United States, 02115
United States, Oregon
Oregon Health & Science University OHSU 2
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)
Bethlehem, Pennsylvania, United States
United States, South Carolina
Cancer Centers of the Carolinas CCC Faris
Greenville, South Carolina, United States, 29605
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Gera, Germany, 07548
Novartis Investigative Site
Kiel, Germany, 24105
Novartis Investigative Site
Muenchen, Germany, 80336
Italy
Novartis Investigative Site
Genova, GE, Italy, 16132
Novartis Investigative Site
Napoli, Italy, 80131
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Maastricht, Netherlands, 5800
Novartis Investigative Site
Nijmegen, Netherlands, 6525 GA
Switzerland
Novartis Investigative Site
Chur, Switzerland, 7000
Novartis Investigative Site
Zürich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 6, 2014
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 September 18, 2014