Trial Outcomes & Findings for Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma (NCT NCT00788775)

Last Updated: 2018-11-15

Results Overview

4-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.

Results posted on

2018-11-15

Participant Flow

The study was activated on January 23, 2009 and closed early in December 2011 due to slow accrual. Patients enrolled from 8 medical centers beginning March 2009 through June 2011.

Participant milestones

Participant milestones
Measure	No CNS Metastastic Cohort Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Overall Study STARTED	11	9
Overall Study Treated	11	8
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Reasons for withdrawal
Measure	No CNS Metastastic Cohort Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Overall Study Progressive Disease	8	6
Overall Study Withdrawal by Subject	0	2
Overall Study Patient Non-Compliance	1	0
Overall Study Patient's measurable disease resected.	1	0

Baseline Characteristics

Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	No CNS Metastastic Cohort n=11 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	Total n=19 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	60 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Melanoma Type Acral	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Melanoma Type Mucosal	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Melanoma Type Chronically Sun-Damaged (CSD)	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
ECOG Performance Status ECOG PS0	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
ECOG Performance Status ECOG PS1	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
ECOG Performance Status ECOG PS2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
CNS Metastatic Status CNS Metastaic: No	11 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants
CNS Metastatic Status CNS Metastaic: Yes	0 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.

Population: The analysis dataset is comprised of treated patients.

Outcome measures

Outcome measures
Measure	No CNS Metastastic Cohort n=11 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
4-month Progression-Free Survival Rate	0.27 proportion of patients Interval 0.08 to 0.56	0.125 proportion of patients Interval 0.006 to 0.47

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).

Population: The analysis dataset is comprised of treated patients.

Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	No CNS Metastastic Cohort n=11 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Progression-Free Survival	3.4 months Interval 0.9 to 5.5	2.4 months Interval 1.8 to 3.9

SECONDARY outcome

Timeframe: Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m).

Population: The analysis dataset is comprised of treated patients.

Overall survival (OS) is defined as the time from study entry to death or date last known alive.

Outcome measures

Outcome measures
Measure	No CNS Metastastic Cohort n=11 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Overall Survival	14.2 months Interval 7.1 to The upper limit of the 90% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	4.3 months Interval 3.5 to 11.9

SECONDARY outcome

Best overall response (BOR) on treatment was based on RECIST 1.0 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation required within 4 weeks. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. CR is disappearance of all non-target lesions.

Outcome measures

Outcome measures
Measure	No CNS Metastastic Cohort n=11 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 Participants Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Best Overall Response Progressive Disease	4 participants	1 participants
Best Overall Response Unevaluable	1 participants	1 participants
Best Overall Response Complete Response	0 participants	0 participants
Best Overall Response Partial Response	2 participants	0 participants
Best Overall Response Stable Disease	4 participants	6 participants

Adverse Events

No CNS Metastastic Cohort

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

CNS Metastatic Cohort

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	No CNS Metastastic Cohort n=11 participants at risk Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.	CNS Metastatic Cohort n=8 participants at risk Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.
Hepatobiliary disorders Hepatic-other	9.1% 1/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	0.00% 0/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations ALT, SGPT	9.1% 1/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	0.00% 0/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations AST, SGOT	9.1% 1/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	0.00% 0/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hyponatremia	9.1% 1/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	0.00% 0/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Skin and subcutaneous tissue disorders Rash/desquamation	9.1% 1/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	0.00% 0/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Lipase	0.00% 0/11 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.	12.5% 1/8 • AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m). Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Other adverse events

Additional Information

F. Stephen Hodi, MD

Dana-Farber Cancer Institute

Phone: 617.632.5053

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place