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

Melanoma Clinical Trial

— TEAM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01028222
• Other study ID #: CAMN107B2301
• Secondary ID: 2009-015514-21
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2009
• Last updated: November 30, 2015
• Start date: June 2010
• Est. completion date: December 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Ministry of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaChina: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesItaly: National Institute for HealthNetherlands: Medicines Evaluation Board (MEB)Poland: Ministry of HealthSingapore: Health Sciences AuthoritySpain: Ministry of HealthSweden: Medical Products AgencySwitzerland: SwissmedicThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Nilotinib
Nilotinib was provided as 200 mg hard gelatin capsules for oral use.
• DTIC
DTIC was supplied locally as sterile powder for i.v. infusion.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	East Melbourne	Victoria
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	North Sydney	New South Wales
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Leuven
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
China	Novartis Investigative Site	Beijing
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Tübingen
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Meldola	FC
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Siena	SI
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Nijmegen
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Cataluña
Sweden	Novartis Investigative Site	Goteborg
Sweden	Novartis Investigative Site	Malmö
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Zürich
United States	University of Colorado Univ Colorado 2	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology	Baltimore	Maryland
United States	Dana Farber Cancer Institute DFCI - Brookline	Boston	Massachusetts
United States	Rush University Medical Center SC	Chicago	Illinois
United States	Case Western Reserve Case Western	Cleveland	Ohio
United States	Baylor Health Care System/Sammons Cancer Center Baylor 2	Dallas	Texas
United States	City of Hope National Medical Center City of Hope national Med Ctr	Duarte	California
United States	University of California San Diego - Moores Cancer Center UCSD Moores Cancer Center	La Jolla	California
United States	University of California at Los Angeles UCLA	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oncology Specialists, SC Dept.of Oncology Specialists	Park Ridge	Illinois
United States	Mayo Clinic - Rochester Mayo Clinic- Gonda	Rochester	Minnesota
United States	California Pacific Medical Center California Pacific Med	San Francisco	California
United States	Washington University School of Medicine CAMN107B2301	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Germany,  Italy,  Netherlands,  Singapore,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

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