A Phase 2 interventional study of Nilotinib and DTIC in Melanoma, sponsored by Novartis Pharmaceuticals. Completed at 49 sites in 14 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-12-30.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Prevention
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.
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.
3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.
This study's enrollment of 55 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.
Browse Melanoma studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may have applied.
400 mg twice daily
Drug: Nilotinib
850 mg/m2 IV every 3 weeks
Drug: DTIC
Nilotinib was provided as 200 mg hard gelatin capsules for oral use.
Also known as: AMN107
DTIC was supplied locally as sterile powder for i.v. infusion.
Also known as: Dacarbazine
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.
Time frame: End of study (up to 39 months)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: End of study (up to 39 months)
| Milestone | Nilotinib | DTIC |
|---|---|---|
| Started | 42 | 13 |
| Cross over from dtic to nilotinib | 0 | 10 |
| Completed | 4 | 0 |
| Not completed | 38 | 13 |
| Withdrew: Protocol deviation | 1 | 0 |
| Withdrew: Disease progression | 33 | 9 |
| Withdrew: Administrative problems | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Crossover to nilotinib w/out progression | 0 | 2 |
| Withdrew: Adverse event | 2 | 0 |
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.
| Participants | Nilotinib | DTIC |
|---|---|---|
| Overall Response Rate (ORR) | 11 | 3 |
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.
| Participants | Nilotinib | DTIC |
|---|---|---|
| Durable Overall Response Rate (DORR) | 11 | 3 |
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.
| Months | Nilotinib | DTIC |
|---|---|---|
| Progression Free Survival (PFS) | 4.2 (2.1 to 5.8) | 4.2 (0.8 to 8.0) |
OS was defined as the time from the date of the start of treatment to the date of death due to any cause.
| Months | Nilotinib | DTIC |
|---|---|---|
| Overall Survival (OS) | 18.0 (10.9 to 20.3) | 22.8 (4.9 to NA) |
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.
| months | Nilotinib | DTIC |
|---|---|---|
| Time to Objective Response (TOR) | NA (NA to NA) | NA (NA to NA) |
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.
| Participants | Nilotinib | DTIC |
|---|---|---|
| Disease Control Rate (DCR) | 20 | 7 |
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.
| Percentage of participants | Nilotinib | DTIC |
|---|---|---|
| PFS Rate | 34.6 | 23.1 |
OS was defined as the time from the date of the start of treatment to the date of death due to any cause.
| Percentage of participants | Nilotinib | DTIC |
|---|---|---|
| OS Rate | 63.6 | 66.7 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nilotinib | — | 12/42 (28.6%) | 40/42 (95.2%) |
| DTIC | — | 1/13 (7.7%) | 9/13 (69.2%) |
| Crossover Nilotinib Treatment | — | 4/10 (40%) | 10/10 (100%) |
| Event | Nilotinib | DTIC | Crossover Nilotinib Treatment |
|---|---|---|---|
| ArrhythmiaCardiac disorders | 0/42 | 0/13 | 1/10 |
| Myocardial infarctionCardiac disorders | 0/42 | 0/13 | 1/10 |
| Retinal detachmentEye disorders | 0/42 | 0/13 | 1/10 |
| Abdominal painGastrointestinal disorders | 2/42 | 0/13 | 1/10 |
| AscitesGastrointestinal disorders | 0/42 | 0/13 | 1/10 |
| General physical health deteriorationGeneral disorders | 0/42 | 0/13 | 1/10 |
| Oedema peripheralGeneral disorders | 0/42 | 0/13 | 1/10 |
| Herpes zoster cutaneous disseminatedInfections and infestations | 0/42 | 0/13 | 1/10 |
| InfectionInfections and infestations | 0/42 | 0/13 | 1/10 |
| HyperglycaemiaMetabolism and nutrition disorders | 0/42 | 0/13 | 1/10 |
| Event | Nilotinib | DTIC | Crossover Nilotinib Treatment |
|---|---|---|---|
| RashSkin and subcutaneous tissue disorders | 20/42 | 2/13 | 3/10 |
| Blood bilirubin increasedInvestigations | 19/42 | 1/13 | 3/10 |
| NauseaGastrointestinal disorders | 18/42 | 5/13 | 2/10 |
| FatigueGeneral disorders | 13/42 | 5/13 | 4/10 |
| HeadacheNervous system disorders | 6/42 | 5/13 | 3/10 |
| Decreased appetiteMetabolism and nutrition disorders | 13/42 | 2/13 | 3/10 |
| DiarrhoeaGastrointestinal disorders | 7/42 | 1/13 | 3/10 |
| AstheniaGeneral disorders | 2/42 | 1/13 | 3/10 |
| HyperglycaemiaMetabolism and nutrition disorders | 9/42 | 1/13 | 3/10 |
| CoughRespiratory, thoracic and mediastinal disorders | 9/42 | 2/13 | 3/10 |
| Age, Continuous(Years) | Nilotinib | DTIC | Total |
|---|---|---|---|
| Mean | 64.7 ± 12.39 | 68.8 ± 12.99 | 66.8 ± 12.69 |
| Sex: Female, Male(Participants) | Nilotinib | DTIC | Total |
|---|---|---|---|
| Female | 23 | 8 | 31 |
| Male | 19 | 5 | 24 |
This study is completed, as verified in Nov 2015. You cannot join it, but the record below documents what was studied.
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Novartis Pharmaceuticals