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 BRAFV600E or NRAS mutations - ND

OVARTIS FARMA0 sites54 target enrollmentMay 18, 2011

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Not specified
Sponsor: OVARTIS FARMA
Enrollment: 54
Status: Active, not recruiting
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 18, 2011

End Date

TBD

Last Updated

13 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

OVARTIS FARMA

Eligibility Criteria

Inclusion Criteria

•1\. Male or female patients age \= 18 years 2\. Histologically confirmed diagnosis of locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery (Appendix 1\) 3\. Must have documented presence of somatic BRAFV600E\* or NRAS mutation in tumor tissue (\*melanoma histologies positive for other activating BRAF mutations may be considered upon approval by the Novartis Medical Monitor). 4\. All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable central confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol 5\. Evidence of measurable tumor disease as per RECIST (Appendix 2\), defined as at least one lesion that can accurately be measured in at least one dimension as \= 20 mm by conventional radiological technique or \= 10 mm with spiral CT\-scan. Cutaneous lesions must have clearly defined margins and measure \= 5 mm in at least one diameter and be documented by color photography. Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression in such lesions. 6\. WHO performance status of 0\-2 7\. Adequate organ function and laboratory parameters as defined in teh protocol 8\. Recovery from all reversible adverse events of previous anti\-cancer therapies to baseline or to Grade \= 1, except for alopecia and Grade \<2 sensory PNP 9\. LVEF \= 50% as determined by MUGA scan or TTE 10\. Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow\-up) and be within geographical proximity to make the required study visits 11\. Negative serum ß\-HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose 12\. Written informed consent obtained prior to any screening procedures.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1\.2 Adults (18\-64 years) yes
•F.1\.2\.1 Number of subjects for this age range
•F.1\.3 Elderly (\>\=65 years) yes
•F.1\.3\.1 Number of subjects for this age range

Exclusion Criteria

•1\. History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO 2\. Patients with CNS metastasis unless previously treated with surgery, whole\-brain radiation or stereotactic radiosurgery and the disease has been stable for at least 2 months without steroid use or on a stable dose of steroids for at least 1 month prior to the first dose of MEK162 3\. Prior therapy with a MEK\- inhibitor 4\. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: • History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) \<6 months prior to screening • Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality • Uncontrolled arterial hypertension, defined as BP \> 140/100 mmHg (average of 3 consecutive readings) 5\. Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C infection 6\. Any other condition that would, in the Investigator’s judgment, contraindicate patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures , e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc. 7\. Patients who have received prior systemic anti\-cancer treatment within the following time frames: • Patients who have received cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin\-C) prior to starting study drugs • Patients who have received biologic therapy (e.g., antibodies) within 4 weeks prior to starting study drug • Patients who have been treated with continuous or intermittent small molecule therapeutics within \= 5 t1/2 of the agent, or \= 4 weeks prior to starting study drug where half life is unknown • Patients who have received any other investigational agents within a period of time that is less than the cycle length used for that treatment or \= 4 weeks (whichever is shorter) prior to starting study drugs • Treatment with prior radiotherapy within 28 days of the first dose of study drug; however, if the radiation portal covered \= 10% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy 8\. Patients who have undergone major surgery \= 4 weeks prior to starting study drug or who have not recovered from side effects of such procedure 9\. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL) 10\. Women of child\-bearing potential, defined as all women physiologically capable of becoming pregnant. See protocol for further details. 11\. Medical, psychiatric, cognitive or other conditions that may compromise the patient\`s ability to understand the patient information, give informed consent, comply with the study protocol or complete the study. UNLESS they are: