MelanomaPhase 2TEAMNCT01028222
A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation
A Phase 2 study testing Nilotinib and DTIC in people with Melanoma, run by Novartis Pharmaceuticals at 49 sites in 14 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nilotinib and DTIC
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 49 sitesin 14 countries
- Study dates
- Jun 2010to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
- Patients with c-Kit amplifications only and no mutation
- Patients with any history of brain metastases
- Patients who have had any prior treatment with TKIs
- Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit
- Acute or chronic liver or renal disease considered unrelated to melanoma
- Other protocol-defined inclusion/exclusion criteria may have applied.
Trial locations and contacts
49 sites in 14 countries.
49 sites in 14 countries
United States14 sites
University of Colorado Univ Colorado 2
Aurora, Colorado, 80045
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Medical Oncology
Baltimore, Maryland, 21231
Dana Farber Cancer Institute DFCI - Brookline
Boston, Massachusetts, 02215
Rush University Medical Center SC
Chicago, Illinois, 60612
Case Western Reserve Case Western
Cleveland, Ohio, 44106-5000
Baylor Health Care System/Sammons Cancer Center Baylor 2
Dallas, Texas, 75246
City of Hope National Medical Center City of Hope national Med Ctr
Duarte, California, 91010-3000
University of California San Diego - Moores Cancer Center UCSD Moores Cancer Center
La Jolla, California, 92093-0658
University of California at Los Angeles UCLA
Los Angeles, California, 90024
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Oncology Specialists, SC Dept.of Oncology Specialists
Park Ridge, Illinois, 60068-0736
Mayo Clinic - Rochester Mayo Clinic- Gonda
Rochester, Minnesota, 55905
California Pacific Medical Center California Pacific Med
San Francisco, California, 94120-7999
Washington University School of Medicine CAMN107B2301
St Louis, Missouri, 63110
Italy6 sites
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Meldola, FC, 47014
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Padova, PD, 35100
Novartis Investigative Site
Siena, SI, 53100
Germany5 sites
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
München, 80336
Novartis Investigative Site
Tübingen, 72076
Australia4 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
East Melbourne, Victoria, 3002
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
North Sydney, New South Wales, 2060
Sweden4 sites
Novartis Investigative Site
Gothenburg, SE-413 45
Novartis Investigative Site
Malmö, SE-205 02
Novartis Investigative Site
Stockholm, SE-171 76
Novartis Investigative Site
Uppsala, SE-751 85
Belgium3 sites
Novartis Investigative Site
Brussels, 1090
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Leuven, 3000
Brazil3 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-281
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20230-130
Novartis Investigative Site
São Paulo, São Paulo, 01246-000
Canada2 sites
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, M5G 1Z5
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1081 HV
Novartis Investigative Site
Nijmegen, 6525 GA
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Argentina1 site
Novartis Investigative Site
Buenos Aires, Buenos Aires, C1125ABE
About this study
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
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- Nilotinib, DTIC
- Keywords
- Melanoma, AMN107, c-Kit, c-Kit mutated metastatic and/or inoperable melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called AMN107
Nilotinib was provided as 200 mg hard gelatin capsules for oral use.
DTICDrug
Also called Dacarbazine
DTIC was supplied locally as sterile powder for i.v. infusion.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | 400 mg twice daily Receives: Drug: Nilotinib |
| DTIC | Active comparator | 850 mg/m2 IV every 3 weeks Receives: Drug: DTIC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of study (up to 39 months)
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: End of study (up to 39 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startJun 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01028222
- Sponsor's protocol ID
- CAMN107B2301
- Other IDs
- 2009-015514-21, 2009
- Acronym
- TEAM
- Status last verified
- Nov 2015
- First submitted
- 7 Dec 2009
- Last updated
- 30 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 28327988
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study 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
- ClinicalTrials.gov ID
- NCT01028222
- Acronym / sponsor ID
- TEAM / CAMN107B2301
- Conditions
- Melanoma
- Keywords
- Melanoma, AMN107, c-Kit, c-Kit mutated metastatic and/or inoperable melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 9 Dec 2009 (estimated)
- Results
- Posted 26 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: Nilotinib400 mg twice daily |
| DTIC | Active comparator | Drug: DTIC850 mg/m2 IV every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (7 listed)
- C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
- Patients with c-Kit amplifications only and no mutation
- Patients with any history of brain metastases
- Patients who have had any prior treatment with TKIs
- Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibAlso: AMN107Nilotinib was provided as 200 mg hard gelatin capsules for oral use. | Drug | Nilotinib |
| DTICAlso: DacarbazineDTIC was supplied locally as sterile powder for i.v. infusion. | Drug | DTIC |
Primary outcome
Overall Response Rate (ORR)
Time frame: End of study (up to 39 months)
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.
7 secondary outcomes
Durable Overall Response Rate (DORR)
Time frame: End of study (up to 39 months)
Progression Free Survival (PFS)
Time frame: End of study (up to 39 months)
Overall Survival (OS)
Time frame: End of study (up to 39 months)
Time to Objective Response (TOR)
Time frame: End of study (up to 39 months)
Disease Control Rate (DCR)
Time frame: End of study (up to 39 months)
PFS Rate
Time frame: End of study (up to 39 months)
OS Rate
Time frame: End of study (up to 39 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28327988Guo 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
49 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib and DTIC in people with Melanoma, run by Novartis Pharmaceuticals at 49 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Italy, Germany, Australia, Sweden and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: End of study (up to 39 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01028222, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2015.