The TEAM Trial (Tasigna Efficacy in Advanced Melanoma): A phase II,open label, multi-center, single-arm study to assess the efficacy ofTasigna ® in the treatment of patients with metastatic and/orinoperable melanoma harboring a c-Kit mutation.

• Conditions: treatment of patients with metastatic and/or inoperable melanoma harboring a c-Kit mutation; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 14.1Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864

• Registration Number: EUCTR2009-015514-21-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-12
• Last Update Posted: 16 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1.Histologically confirmed mucosal or acral melanoma.
2.Presence of a c-Kit mutation of exon 9, 11 or 13, or mutations D820G, N822H, N822K, D820Y, Y822D or Y823D of exon 17, as confirmed by the central laboratory.
3.Stage III unresectable or stage IV disease.
4.The presence of one or more measurable lesions as detected by radiological or photographic methods and assessed according to RECIST. Lesions must have a size of at least 10mm at longest diameter (using a slice thickness of 5 mm) or double the slice thickness to be considered a target lesion. Target lesion should not be selected in previously irradiated fields unless there is clear evidence of progression.
5.WHO performance status 0 - 2.
6.At least 28 days since major surgery prior to study drug.
7.Age 18 or greater.
8.Patients must have adequate bone marrow and organ function as defined by the following laboratory values:
•Serum potassium within the normal limits or corrected to within normal limits with supplements
•Total calcium (corrected for serum albumin) within the normal limits or corrected to within normal limits with supplements
•Serum magnesium within the normal limits or corrected to within normal limits with supplements
•Serum phosphate within the normal limits or corrected to within normal limits with supplements
•ALT and AST = 2.5 x ULN (upper limit of normal) or = 5.0 x ULN if considered due to tumor.
•Alkaline phosphatase = 2.5 x ULN or = 5.0 x ULN if considered due to tumor.
•Serum bilirubin = 1.5 x ULN.
•Serum creatinine = 1.5 x ULN
•Serum amylase = 1.5 x ULN and serum lipase = 1.5 x ULN.
•Hemoglobin = 9.0 g/dL, absolute neutrophil count =1.5 x 109/L, platelets =100 x 109/L.
9.The capacity to understand the patient information sheet and the ability to provide written informed consent.
10.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study 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.C-Kit mutation of exons 17 (except mutations D820G, N822H, N822K, D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria.
2.Patients with c-Kit amplifications without mutations.
3.Patients with any history ofbrain metastases.
4.Patients who have had any prior treatment with TKIs.
5.Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit.
6.Impaired cardiac function, including any one of the following:
•LVEF < 45% or below institutional lower limit of the normal range (which ever is higher) as determined by MUGA scan or echocardiogram.
•Complete left bundle branch block.
•Use of a cardiac pacemaker.
•Congenital long QT syndrome.
•History of or presence of significant ventricular or atrial tachyarrhythmias.
•Clinically significant resting bradycardia (< 50 beats per minute).
•QTc > 450 msec on screening ECG (using the QTcF formula).
•Right bundle branch block plus left anterior hemiblock, bifascicular block.
•Myocardial infarction within 12 months prior to enrollment.
•Unstable angina diagnosed or treated during the past 12 months.
•Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
7.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive gastric or small bowel resection).
8.History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
9.Acute or chronic liver or renal disease considered unrelated to melanoma.
10.Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
11.Patients who are currently receiving treatment with any medications that have a significant potential to prolong the QT interval. See link for list of these medications: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm.
12.Patients currently receiving therapy with strong CYP3A4 inhibitors. See link for list of these medications: http://medicine.iupui.edu/flockhart/table.htm.
13.Patients receiving therapy with strong CYP3A4 inducers. See link for list of these medications: http://medicine.iupui.edu/flockhart/table.htm.
14.Patients who have received 2 or more prior regimens of systemic anticancer therapy for melanoma.
15.Patients with no evidence of clear progression of disease, either with or without prior systemic anticancer therapy.
16.Patients with less than 12 weeks between their last dose of an anti-CTLA4 agent (i.e. ipilimumab or tremelimumab) and the Screening/Baseline visit.
17.Patients who have received cytotoxic chemotherapy = 4 weeks (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from the side effects of such therapy.
18.Patients who have received immunotherapy = 1 week prior to starting study drug or who have not recovered from the side effects of such therapy.
19.Patients who have received any investigational drug = 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy.
20.Patients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified