Trial Outcomes & Findings for Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma (NCT NCT00424515)

Last Updated: 2016-12-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m).

Results posted on

2016-12-08

Participant Flow

The study was activated on July 6, 2006 and closed March 1, 2011. Patients enrolled from 9 medical centers beginning April 2007 through December 2010.

Participant milestones

Participant milestones
Measure	Amplified KIT Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Overall Study STARTED	11	13
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	11	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Amplified KIT Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Overall Study Progressive Disease	10	11
Overall Study Adverse Event	0	1
Overall Study Intercurrent Illness	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amplified KIT n=11 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT n=13 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Total n=24 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	64 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	13 participants n=7 Participants	24 participants n=5 Participants
Melanoma Type Acral	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Melanoma Type Mucosal	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants
Melanoma Type Chronically Sun-Damaged	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m).

Population: The analysis dataset is comprised of treated patients.

Outcome measures

Outcome measures
Measure	Amplified KIT n=11 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT n=13 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Best Overall Response Partial Response	0 participants	7 participants
Best Overall Response Stable Disease	2 participants	3 participants
Best Overall Response Progressive Disease	9 participants	3 participants
Best Overall Response Complete Response	0 participants	0 participants

SECONDARY outcome

Timeframe: Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment and every 3 months long-term. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m).

Population: The analysis dataset is comprised of treated patients.

Time to progression (TTP) 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. 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	Amplified KIT n=11 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT n=13 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Time to Progression	3.4 months Interval 1.0 to 5.7	3.9 months Interval 2.6 to 6.6

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 10.6 months (range 3.7-27.1).

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	Amplified KIT n=11 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT n=13 Participants Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Overall Survival	11.9 months Interval 4.5 to 16.2	12.9 months Interval 5.5 to 24.3

Adverse Events

Amplified KIT

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Mutated KIT

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Amplified KIT n=11 participants at risk Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.	Mutated KIT n=13 participants at risk Imatinib was given at a dose of 400 mg orally daily (4 100 mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition. Patients were classified into two cohorts based upon KIT molecular status.
Blood and lymphatic system disorders Hemoglobin	0.00% 0/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	15.4% 2/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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 Hypokalemia	0.00% 0/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	7.7% 1/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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 Leukocytes	0.00% 0/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	7.7% 1/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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 Lymphopenia	9.1% 1/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	7.7% 1/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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 Neutrophils	0.00% 0/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	7.7% 1/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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 Pruritus/itching	0.00% 0/11 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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.	7.7% 1/13 • AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment. 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