Clinical trial NCT01028222: A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: Melanoma
AMN107
c-Kit
c-Kit mutated metastatic and/or inoperable melanoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-12-09
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether nilotinib is efficacious in the treatment of metastatic and/or inoperable melanoma harboring a c-Kit mutation.

Detailed description: This trial began as a multi-center, randomized, Phase III, controlled trial for nilotinib vs (DTIC) dacarbazine to assess the efficacy and safety of nilotinib (400 mg bid) in patients with c-Kit mutated metastatic and/or inoperable melanoma. The study was open to patients with mucosal or acral melanoma.

Due to substantial difficulties identifying and recruiting eligible patients, the trial design was altered from a randomized, two-arm, Phase III study to a single-arm, Simon two-stage Phase II study with protocol Amendment 2 (27-Jul-2011). While the original protocol required the recruitment of 120 patients, this amendment required the study to recruit only 41 patients (patients randomized to nilotinib prior to Amendment 2 were to be counted in this total, but those randomized to dacarbazine ( DTIC ) DTIC were not). Patients randomized to DTIC were allowed to cross-over to nilotinib, either immediately or at the time of progression.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed mucosal or acral 2. Presence of a c-Kit mutation of exon 9, 11 or 13, or mutations Y822D and mutations D820Y, 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 1.0. 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 lesions should not be selected in previously irradiated fields unless there is clear evidence of progression 5. WHO performance status 0 - 2

Exclusion Criteria:

1. C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
2. Patients with c-Kit amplifications only and no mutation
3. Patients with any history of brain 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. Acute or chronic liver or renal disease considered unrelated to melanoma

Other protocol-defined inclusion/exclusion criteria may have applied.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: End of study (up to 39 months)
Secondary outcomes:
measure: Durable Overall Response Rate (DORR)
timeFrame: End of study (up to 39 months)
measure: Progression Free Survival (PFS)
timeFrame: End of study (up to 39 months)
measure: Overall Survival (OS)
timeFrame: End of study (up to 39 months)
measure: Time to Objective Response (TOR)
timeFrame: End of study (up to 39 months)
measure: Disease Control Rate (DCR)
timeFrame: End of study (up to 39 months)
measure: PFS Rate
timeFrame: End of study (up to 39 months)
measure: OS Rate
timeFrame: End of study (up to 39 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center City of Hope national Med Ctr
state: California
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center California Pacific Med
state: California
city: Aurora
country: United States
facility: University of Colorado Univ Colorado 2
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center SC
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC Dept.of Oncology Specialists
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute DFCI - Brookline
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester Mayo Clinic- Gonda
state: Minnesota
city: St. Louis
country: United States
facility: Washington University School of Medicine CAMN107B2301
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve Case Western
state: Ohio
city: Dallas
country: United States
facility: Baylor Health Care System/Sammons Cancer Center Baylor 2
state: Texas
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: North Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Beijing
country: China
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Köln
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Malmö
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Zürich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Guo J, Carvajal RD, Dummer R, Hauschild A, Daud A, Bastian BC, Markovic SN, Queirolo P, Arance A, Berking C, Camargo V, Herchenhorn D, Petrella TM, Schadendorf D, Sharfman W, Testori A, Novick S, Hertle S, Nourry C, Chen Q, Hodi FS. Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial. Ann Oncol. 2017 Jun 1;28(6):1380-1387. doi: 10.1093/annonc/mdx079.