A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation (TEAM)

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Nilotinib; Drug: DTIC

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABE
    • Novartis Investigative Site
• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Novartis Investigative Site
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-281
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20230-130
      • Novartis Investigative Site
  • SP
    • São Paulo, SP, Brazil, 01246-000
      • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 1Z5
      • Novartis Investigative Site
• China
  • Beijing, China, 100036
    • Novartis Investigative Site
• Germany
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Köln, Germany, 50937
    • Novartis Investigative Site
  • Muenchen, Germany, 80336
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
• Italy
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6525 GA
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Cataluña
    • Hospitalet de LLobregat, Cataluña, Spain, 08907
      • Novartis Investigative Site
• Sweden
  • Goteborg, Sweden, SE-413 45
    • Novartis Investigative Site
  • Malmö, Sweden, SE-205 02
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
• Switzerland
  • Zürich, Switzerland, 8091
    • Novartis Investigative Site
• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center City of Hope national Med Ctr
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90024
      • University of California at Los Angeles UCLA
    • San Francisco, California, United States, 94120-7999
      • California Pacific Medical Center California Pacific Med
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Univ Colorado 2
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center SC
    • Park Ridge, Illinois, United States, 60068-0736
      • Oncology Specialists, SC Dept.of Oncology Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute DFCI - Brookline
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester Mayo Clinic- Gonda
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine CAMN107B2301
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106-5000
      • Case Western Reserve Case Western
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Health Care System/Sammons Cancer Center Baylor 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib; 400 mg twice daily	Drug: Nilotinib; Nilotinib was provided as 200 mg hard gelatin capsules for oral use.; Other Names: AMN107
Active Comparator: DTIC; 850 mg/m2 IV every 3 weeks	Drug: DTIC; DTIC was supplied locally as sterile powder for i.v. infusion.; Other Names: Dacarbazine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the proportion of participants with a best overall response (BOR) of a confirmed complete response or partial response (CR+PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) based on local investigators' assessment (CT/MRI/photography). Per RECIST, CR: disappearance of all target lesions, all non-target lesions, and no new lesion; PR: a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no unequivocal progression of non-TLs, and no new lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments at least 4 weeks apart.	End of study (up to 39 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durable Overall Response Rate (DORR)	DORR was defined as the rate of best overall response (CR+PR) lasting at least 12 weeks determined by RECIST v1.0 based on local investigators' assessment (CT/MRI/photography). The duration of ORR responders is computed from the date of first documented response (CR/PR) to the date of first documented progression or death due to underlying disease. Per RECIST, CR: disappearance of all target lesions, all non-target lesions, and no new lesion; PR: a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments at least 4 weeks apart.	End of study (up to 39 months)
Progression Free Survival (PFS)	PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined using RECIST v1.0, as a >=20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or unequivocal progression of non-target lesions.	End of study (up to 39 months)
Overall Survival (OS)	OS was defined as the time from the date of the start of treatment to the date of death due to any cause.	End of study (up to 39 months)
Time to Objective Response (TOR)	TOR was defined as the time between the start date of treatment until first documented confirmed response of CR or PR determined by RECIST v1.0 based on local investigators' assessment (CT/MRI/photography). Per RECIST, CR: disappearance of all target lesions, all non-target lesions, and no new lesion; PR: a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no unequivocal progression of non-TLs, and no new lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments at least 4 weeks apart.	End of study (up to 39 months)
Disease Control Rate (DCR)	DCR was defined as the proportion of participants with an overall response of CR of any duration, PR of any duration, or stable disease (SD) for a minimum of 12 weeks from start of treatment. Per RECIST, CR: disappearance of all target lesions, all non-target lesions, and no new lesion; PR: a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no unequivocal progression of non-TLs, and no new lesions; PD, a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; SD: no change or small changes that do not meet previously given criteria for CR, PR or PD.	End of study (up to 39 months)
PFS Rate	PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined using RECIST v1.0, as a >=20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or unequivocal progression of non-target lesions.	End of study (up to 39 months)
OS Rate	OS was defined as the time from the date of the start of treatment to the date of death due to any cause.	End of study (up to 39 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: December 7, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (Estimate): December 9, 2009

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Melanoma; AMN107; c-Kit; c-Kit mutated metastatic and/or inoperable melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine
• Other Study ID Numbers: CAMN107B2301; 2009-015514-21 (EudraCT Number)