Clinical Trials Register

Summary
EudraCT Number:	2009-015514-21
Sponsor's Protocol Code Number:	CAMN107B2301
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-04-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2009-015514-21

A.3

Full title of the trial

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

A.4.1

Sponsor's protocol code number

CAMN107B2301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01028222

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice
B.5.3	Address:
B.5.3.1	Street Address	Roonstr. 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49180223 23 00
B.5.5	Fax number	+49911273 12160
B.5.6	E-mail	infoservice.novartis@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tasigna 200 mg Hartkapseln
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/06/375
D.3 Description of the IMP
D.3.1	Product name	Tasigna
D.3.2	Product code	B2301
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	nilotinib
D.3.9.1	CAS number	641571-10-0
D.3.9.2	Current sponsor code	CAMN107B2301
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

treatment of patients with metastatic and/or inoperable melanoma harboring a c-Kit mutation

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10027481
E.1.2	Term	Metastatic melanoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the clinical efficacy of nilotinib, based on overall response rate (ORR), in the treatment of c-Kit mutated melanoma in patients who have not received prior therapy with TKIs.

E.2.2

Secondary objectives of the trial

Key secondary objectives
•To assess the durable overall response rate (DORR) of patients treated with nilotinib.
•To assess progression free survival (PFS) of patients treated with
nilotinib.
•To assess overall survival (OS) of patients treated with nilotinib.
•To assess the time to objective response (TOR) and duration of overall response (DOR) from nilotinib treatment.
•To assess the disease control rate (DCR) from nilotinib treatment.
•To assess the PFS rate at 6 months (PFS6) and OS rate at 12 months (OS12) for nilotinib treatment.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
21.Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
22.Women who are pregnant, breast feeding or adults of reproductive potential not employing an effective method of birth control. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients must agree to employ an effective method of contraception during the study and for up to three months following discontinuation from the study. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.

E.5 End points

E.5.1

Primary end point(s)

The ORR, calculated as the proportion of patients with a best overall response of confirmed complete response or partial response (CR+PR).

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary analysis: when all patients have reached 24 weeks or have
discontinued

E.5.2

Secondary end point(s)

•DORR, calculated as the rate of patients with a CR or PR lasting equal to or more than 12 weeks.
•PFS, defined as the time from initiation of study drug to the first
documented progression or death due to any cause.
•OS, defined as the time from initiation of study drug to death due to any cause.
•TOR, calculated as the time from date of initiation of study drug until first documented response of CR or PR.
•DOR, calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer.
•DCR, calculated as the proportion of patients with a best overall
response of CR, PR or stable disease (SD) for a minimum of 12 weeks from date of initiation of study drug.
•PFS6
•OS12

E.5.2.1

Timepoint(s) of evaluation of this end point

Primary analysis: when all patients have reached 24 weeks or have
discontinued

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Brazil

Canada

China

Singapore

Switzerland

Thailand

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2010-04-12.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients continuing to derive benefit from the study treatment at the end of the study in the opinion of the investigator will be eligible to continue into a roll-over study in order to receive treatment with nilotinib for as long as they continue to demonstrate benefit and do notexperience unacceptable toxicities or until nilotinib becomes available to the patient or the nilotinib development program is stopped (whichever comes first)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-06-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-31

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