Clinical trial NCT00424515: Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma
Official title: A Phase II Study of Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma and Melanomas That Arise on Chronically Sun Damaged Skin.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mucosal Melanoma
Acral/Lentiginous Melanoma
Chronically Sun Damaged Melanomas
Keywords: Imatinib
Gleevec
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-01-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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:

* 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

Primary outcomes:
measure: Best Overall Response
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).
Secondary outcomes:
measure: Time to Progression
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).
measure: Overall Survival
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).
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado at Denver Health Sciences Center
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: F. Stephen Hodi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.