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CompletedNCT00424515BUS255Updated Dec 8, 2016Results posted

Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

A Phase 2 interventional study of Imatinib in Mucosal Melanoma, Acral/Lentiginous Melanoma and Chronically Sun Damaged Melanomas, sponsored by Dana-Farber Cancer Institute. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-12-08.

Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
24
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate how effective imatinib (Gleevec) is in treating acral/lentiginous and mucosal melanoma which has spread to other parts of the body in patients who's disease carries a c-kit mutation. Imatinib is a protein-kinase inhibitor. It is believed that imatinib may be effective in blocking signals on certain cancer cells which allow the malignant cells to multiply and spread.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the response rate of patients with metastatic mucosal, acral/lentiginous, or chronically sun damaged melanomas to treatment with of imatinib.
  • To determine the time to progression.

Secondary

  • To correlate c-kit mutational status with response to therapy.
  • To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
  • Tolerability of imatinib.
  • To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.
  • To correlate c-kit amplification status with response to therapy.
02

Conditions studied

  • Mucosal Melanoma
  • Acral/Lentiginous Melanoma
  • Chronically Sun Damaged Melanomas

Keywords

  • Imatinib
  • Gleevec
03

In context

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 832 studies on the registry; 122 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Browse Dana-Farber Cancer Institute studies →

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Melanomas that arise on chronically sun damaged skin and have pathologic evidence of solar elastosis
  • History of primary mucosal or acral/lentiginous melanoma
  • Histologically documented stage IV metastatic melanoma
  • ECOG performance status 0,1, or 2
  • Estimated life expectancy of 6 months or greater
  • Age 18 years or older
  • Creatinine \< 1.5 x ULN
  • ANC > 1500 ul
  • Platelets > 100,000 ul
  • Total bilirubin, AST, and ALT \< 2 x ULN
  • Amylase and lipase \< 1.5 x ULN
  • C-kit mutation documented from either primary or metastatic tumor site
  • > 4 weeks from prior chemotherapy or investigational drug
  • At least one measurable site of disease as defined by at least 1 cm in greatest dimension

Exclusion criteria

Exclusion Criteria:

  • Severe and/or uncontrolled medical disease
  • Pregnant or nursing mothers
  • Any other significant medical, surgical, or psychiatric condition that my interfere with compliance
  • Patient is \< 5 years free of another primary malignancy except: basal cell skin cancer or a cervical carcinoma in situ
  • Concurrent treatment with Warfarin
  • Prior treatment with c-kit inhibitor
  • Patient with Grade III/IV cardiac problems as defined by NYHA criteria
  • No H2 blockers or proton pump inhibitors
  • Known brain metastasis
  • Known chronic liver disease
  • Known diagnosis of HIV infection
  • Previous radiotherapy to > 25% of the bone marrow
  • Major surgery within 2 weeks prior to study entry
  • Patient has received any other investigational agent within 28 days of first study drug dosing
  • Chemotherapy within 4 weeks prior to study entry
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
24 participants (actual)

Study arms

  • Experimental
    Treatment Arm

    Imatinib

    Drug: Imatinib

Interventions

  • DrugImatinib

    Imatinib was given at a dose of 400 mg orally daily (4 100mg 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.

    Also known as: Gleevec

06

What researchers measure

Primary outcomes

  1. Best Overall Response

    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.

    Time frame: 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).

Secondary outcomes

  1. Time to Progression

    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.

    Time frame: 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).

  2. Overall Survival

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

    Time frame: 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).

07

Results

Posted Dec 8, 2016

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 flow — Overall Study
MilestoneAmplified KITMutated KIT
Started1113
Completed00
Not completed1113
Withdrew: Progressive disease1011
Withdrew: Adverse event01
Withdrew: Intercurrent illness01
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryBest Overall Response

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.

Time frame:
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).
Reported as:
Number · participants
Best Overall Response
participantsAmplified KITMutated KIT
Complete Response00
Partial Response07
Stable Disease23
Progressive Disease93
SecondaryTime to Progression

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.

Time frame:
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).
Reported as:
Median · months
Time to Progression
monthsAmplified KITMutated KIT
Time to Progression3.4 (1.0 to 5.7)3.9 (2.6 to 6.6)
SecondaryOverall Survival

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

Time frame:
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).
Reported as:
Median · months
Overall Survival
monthsAmplified KITMutated KIT
Overall Survival11.9 (4.5 to 16.2)12.9 (5.5 to 24.3)

Adverse events

Collected over AE assessment occurred every other month from the start of study drug and up to day 30 post-treatment.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Amplified KIT—1/11 (9.1%)9/11 (81.8%)
Mutated KIT—3/13 (23.1%)13/13 (100%)
Most frequent serious events
Most frequent serious events
EventAmplified KITMutated KIT
HemoglobinBlood and lymphatic system disorders0/112/13
LymphopeniaInvestigations1/111/13
HypokalemiaMetabolism and nutrition disorders0/111/13
LeukocytesInvestigations0/111/13
NeutrophilsInvestigations0/111/13
Pruritus/itchingSkin and subcutaneous tissue disorders0/111/13
Most frequent other events
Showing 10 of 63
Most frequent other events
EventAmplified KITMutated KIT
FatigueGeneral disorders7/117/13
NauseaGastrointestinal disorders4/118/13
Diarrhea w/o prior colostomyGastrointestinal disorders2/117/13
Edema limbGeneral disorders0/117/13
Edema head and neckGeneral disorders1/116/13
Rash/desquamationSkin and subcutaneous tissue disorders0/114/13
VomitingGastrointestinal disorders2/114/13
AnorexiaMetabolism and nutrition disorders3/112/13
HemoglobinBlood and lymphatic system disorders3/113/13
Taste disturbanceNervous system disorders3/111/13

Baseline characteristics

The analysis dataset is comprised of enrolled and treated patients.

Age, Continuous
Age, Continuous(years)Amplified KITMutated KITTotal
Median69 (55 to 84)64 (42 to 80)65 (42 to 84)
Sex: Female, Male
Sex: Female, Male(Participants)Amplified KITMutated KITTotal
Female71118
Male426
Region of Enrollment
Region of Enrollment(participants)Amplified KITMutated KITTotal
United States111324
Melanoma Type
Melanoma Type(participants)Amplified KITMutated KITTotal
Acral426
Mucosal61117
Chronically Sun-Damaged101
08

Study locations

5 sites
  • University of Colorado at Denver Health Sciences Center
    Denver, Colorado 80045, United States
  • H. Lee Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • University of Chicago
    Chicago, Illinois 60637, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
09

References and documents

Publications

  • Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, Van den Abbeele AD, Demetri GD, Fisher DE. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013 Sep 10;31(26):3182-90. doi: 10.1200/JCO.2012.47.7836. Epub 2013 Jun 17. PubMed 23775962 ↗
  • Zukotynski K, Yap JT, Giobbie-Hurder A, Weber J, Gonzalez R, Gajewski TF, O'Day S, Kim K, Hodi FS, Van den Abbeele AD. Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma. Cancer Imaging. 2014 Nov 12;14(1):30. doi: 10.1186/s40644-014-0030-0. PubMed 25609545 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 8, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00424515
Lead sponsor
Dana-Farber Cancer Institute
Collaborators
Novartis
Responsible party
F. Stephen Hodi, MD (Melanoma Disease Center Director, Dana-Farber Cancer Institute) — Principal investigator
First posted
Jan 19, 2007
Start date
Jul 2006
Primary completion
Jul 2011
Completion
Jul 2011
Results posted
Dec 8, 2016
Last update
Dec 8, 2016

Study contacts

F. Stephen Hodi, MD
principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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