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

March 14, 2011
January 6, 2014
March 2011
June 2014   (final data collection date for primary outcome measure)
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.
estimate the objective response rate (ORR) of MEK162 when administered orally as 45mg twice-daily, to adult patients with advanced, unresectable cutaneous malignant melanoma, harboring BRAFV600E or NRAS mutations. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01320085 on ClinicalTrials.gov Archive Site
  • 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
  • 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. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
  • To characterize safety and tolerability as measured by the frequency and severity of adverse events and changes in laboratory values [ Time Frame: until 30 days after last dose ] [ Designated as safety issue: Yes ]
  • Changes in molecular markers of cell proliferation/survival pre- vs. post-dose tumor tissues and potential correlation with clinical outcomes [ Time Frame: After 15 days of dosing ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma
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

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
BRAF or NRAS Mutant Metastatic Melanoma
Drug: MEK162
  • Experimental: Arm 1
    Intervention: Drug: MEK162
  • Experimental: NRAS mutant, 45mg bid
    45mg bid
    Intervention: Drug: MEK162
  • Experimental: BRAFV600 mutant, 60mg bid
    60mg bid
    Intervention: Drug: MEK162
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
181
June 2014
June 2014   (final data collection date for primary outcome measure)

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.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Netherlands,   Switzerland,   Italy
 
NCT01320085
CMEK162X2201, 2010-023412-13
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP