A Trial Looking at Nilotinib to Treat Acral and Mucosal Melanoma Skin Cancer That Has Spread

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to see if a drug called nilotinib (Tasigna®) is effective in the treatment of patients with a rare group of acral and mucosal melanomas that have a change (mutation) in a protein called cKIT. Nilotinib interferes with signalling inside cells with this mutation and it is believed that this may lead to shrinkage of tumours. Acral melanomas are found on the palms and soles and mucosal melanomas start inside body cavities rather than on the skin.

Detailed Description
-----------------
NICAM has a two step consent process. Patients diagnosed with advanced acral or mucosal melanoma first consent for study registration and undergo screening tests including testing samples of melanoma tissue for the c-KIT mutation. Following confirmation of the c-KIT mutation, patients are asked to consent to study entry with continuation of screening. Eligible patients then enter the study and commence taking nilotinib tablets twice a day for as long as clinical benefit is maintained.

Official Title
-----------------
A Phase II Trial of Nilotinib in the Treatment of Patients With c-KIT Mutated Advanced Acral and Mucosal Melanoma

Conditions
-----------------
Mucosal Lentiginous Melanoma, Acral Lentiginous Malignant Melanoma

Intervention / Treatment
-----------------
* Drug: nilotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with c-KIT mutated histologically proven advanced mucosal or acral melanoma in which the mutation is not known to be associated with nilotinib resistance. Advanced mucosal and acral melanoma defined as unresectable locally advanced or metastatic disease The presence of one or more clinically or radiologically measurable lesions at least 10mm in size Age 18 or greater ECOG performance status 0, 1 or 2 Life expectancy greater than 12 weeks At least 14 days since any major surgery The capacity to understand the patient information sheet and ability to provide written informed consent Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures Women must not be pregnant or lactating with no intention of pregnancy during study treatment. Women of child bearing potential must have a negative serum pregnancy test prior to study entry (even if surgically sterilised). Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) for the duration of the study and should continue such precautions for 6 months after receiving the last study treatment Serum alanine transaminase (ALT) or serum aspartate aminotransferase ≤2.5 x upper limit of normal (ULN) and total serum bilirubin ≤1.5 x ULN Serum creatinine ≤1.5 x ULN Serum lipase and amylase <1.5 x ULN Haemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5 x 109/L, platelets ≥100 x 109/L Prothrombin time (PT) ≤1.5 x ULN Able to swallow and retain oral medication. Exclusion Criteria: Intracranial disease, unless there has been radiological evidence of stable intracranial disease > 6 months. In the case of a solitary brain metastasis, evidence of a disease-free interval of at least 3 months post surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days Women who are pregnant, nursing, or planning to become pregnant during the course of the trial Men who plan to father a child during the course of the trial Use of any investigational drug within 30 days prior to screening (both cancer and non cancer treatments) Use of herbal or chinese medication Use of therapeutic coumarin derivatives (ie warfarin, acenocoumarol, phenprocoumon) Significant cardiac disease including patients who have or who are at significant risk of developing prolongation of QTc Severe and/or uncontrolled medical disease Known chronic liver disease Past medical history of chronic pancreatitis Known HIV infection Previous radiotherapy to 25% or more of the bone marrow Radiation therapy in the 4 weeks prior to study entry Prior exposure to a tyrosine kinase inhibitor Known lactose intolerance Any malabsorption syndrome (i.e. partial gastrectomy, small bowel resection, Crohn's disease or ulcerative colitis).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nilotinib<br>nilotinib 400mgs oral tablets | Drug: nilotinib<br>* nilotinib 400 mgs orally twice daily until disease progression or withdrawal from treatment<br>* Other names: Tasigna;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with the c-KIT mutation who remain progression free at 6 months. | Progression free survival times will be measured from the date of enrolment into the treatment phase until the first date (following start of treatment) of either death or confirmed progressive disease according to RECIST. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicity of treatment | Treatment related toxicity will be assessed at each clinic visit approximately every 4 weeks whilst the patient continues on study treatment. Study treatment will continue until the patient relapses or is withdrawn from study therapy (on average estimated to be between 4 and 52 weeks). | evaluated every 4 weeks whilst the patient is on treatment (on average estimated to be between 4 and 52 weeks) | 
| response at 12 weeks | Lesions must be measured and or evaluated at 12 weeks in accordance with the Response evaluation criteria in solid tumours (RECIST) | tumours measured at 12 weeks from start of treatment | 
| overall survival |  | Expected to be 6 - 12 months (Measured from commencement of treatment until time of death) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
c-KIT mutation, advanced disease, tyrosine kinase inhibitors