Imatinib Mesylate in Treating Patients With Metastatic Melanoma

OBJECTIVES:

- Determine the clinical activity of imatinib mesylate (STI571) in patients with
metastatic melanoma.

- Determine the side effects of this drug in these patients.

- Correlate molecular studies with responsiveness to this drug in these patients.

OUTLINE: Patients receive oral imatinib mesylate (STI571) twice daily. Treatment continues in
the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-78 patients will be accrued for this study within 6-15
months.

Inclusion Criteria:

1. Patient must have a biopsy proven diagnosis of metastatic melanoma. Patients will be
enrolled if at least 20% of the tumor cells stain by immunohistochemistry (see
Appendix E for methodology) for:

1. PDGF receptor alpha or beta, or

2. KIT (CD 117) expression by tumor documented by DAKO antibody staining, or

3. c-abl, ARG.

2. Patients must have measurable indicator metastasis, defined as at least one lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan or
in case of obviously visible cutaneous tumors. Besides the indicator lesion(s), the
patient must have at least one other biopsiable metastasis in a subcutaneous site or
lymph node.

3. Radiographic studies used to assess disease must have been performed within 28 days
prior to registration. If a target lesion has been previously embolized, perfused or
irradiated, there must be objective evidence of progression before start of therapy to
be considered for response assessment.

4. Patient will not have symptomatic central nervous metastases. However, patients with
small asymptomatic metastases will not be excluded provided they are not on steroids
and the lesions are not associated with significant edema. Patients with brain
metastases as the only site of disease are not eligible.

5. Patient may have received prior interferon and/or one other systemic treatment regimen
(chemotherapy, biotherapy, or biochemotherapy). Active immunotherapy (cancer vaccines)
will not be included in the tally of prior treatments.

6. Patient must not have received chemotherapy, biologic therapy or any other
investigational drug for any reason within 28 days prior to registration, and this
extends to 42 days if the patient received a nitrosourea. Patients must not have had a
major surgery within 14 days prior to registration.

7. Patient must have a ECOG performance status < 2 or Karnofsky performance status > 60%
(see Appendix C).

8. Patient must have resolution of transient toxicities from any prior therapy to Grade 1
(NCI-CTC version 2.0, see Appendix B).

9. Patients must have normal organ and marrow function as assessed within 14 days prior
to registration and as defined below:

leukocytes > 3,000/mL absolute neutrophil count > 1,500/mL platelets > 100,000/mL
total bilirubin < 1.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) < 2.5
X institutional upper limit of normal creatinine < 1.5 X institutional upper limit of
normal

10. Patient must have a hemoglobin > 9 gm/dl (this may be achieved by transfusion if
needed) obtained within 14 days prior to registration.

Exclusion Criteria:

11. Patient must not have uncontrolled intercurrent illness including, but not limited to,
ongoing active infection, symptomatic congestive heart failure, myocardial infarction
within 2 months of study, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

12. Patient must not have a severe and/or uncontrolled concurrent medical disease (e.g.,
uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active
uncontrolled infection).

13. Patient must not be pregnant or nursing because Gleevec may be harmful to the
developing fetus and newborn (see Section 3.0 for more detail). Women/men of
reproductive potential must agree to use an effective contraceptive method. Because of
the potential interaction with oral contraceptives both male and female patients of
reproductive potential must agree to employ a barrier method of contraception (condom,
diaphragm) throughout the study and for up to 3 months following discontinuation of
Gleevec.Women of reproductive potential must have a negative serum pregnancy test
within 7 days prior to registration. Post-menopausal women must be amenorrheic for at
least 12 months to be considered of non-childbearing potential.

14. Patient with medical or psychological conditions that, in the opinion of the
investigator, make the patient unable to tolerate or complete the treatment, or to
grant reliable informed consent are not eligible for this study.

15. Patient must not be taking therapeutic doses of coumadin (warfarin) as anticoagulation
at the time of registration. Patients requiring therapeutic anticoagulation may use
low-molecular weight heparin (e.g., Lovenox) or other agents, and mini-dose coumadin
(1 mg po QD) as prophylaxis is allowed.

16. No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease-free for 5 years.