• Progression-free survival measured at 8 weeks after completion of study treatment [ Designated as safety issue: No ]
  

• Overall response rate measured at 6 months [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the clinical efficacy of cilengitide at 2 different doses, in terms of the 8-week progression-free survival rate, in patients with unresectable stage III or stage IV melanoma.

Secondary

• Determine the response rate in patients treated with this drug.
• Determine the overall survival rate of patients treated with this drug.
• Determine the safety and toxicity of this drug in these patients.
• Determine the population pharmacokinetics of this drug in these patients.
• Determine the biological activity of this drug in these patients.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to prior systemic treatment (yes vs no), visceral metastases (yes vs no), serum lactic dehydrogenase level (normal vs abnormal), and tumor integrin α_vβ_3 overexpression (yes vs no). Patients are randomized into 1 of 2 treatment arms.

• Arm I: Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11*, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *For the first course only, treatment is omitted on day 11

• Arm II: Patients receive cilengitide as in arm I at a higher dose. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 26-56 patients (13-28 per treatment arm) will be accrued for this study within 14-20 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed melanoma

  • Unresectable stage III or stage IV disease
  • Cutaneous, mucosal, or unknown origin

• Measurable disease

  • At least one unidimensional lesion ≥ 15 mm by conventional techniques or spiral CT scan
  • In case of obviously visible cutaneous metastatic lesions, at least one unidimensional lesion ≥ 10 mm with clearly defined margins
  • No prior embolization, perfusion, or radiotherapy to target lesion unless there is objective evidence of disease progression
• No metastatic melanoma of choroidal origin

• No known brain metastases

  • Patients who have no radiographical evidence of recurrence in the brain for at least 3 months after prior complete resection of brain metastases OR who have asymptomatic brain metastases that are stable for at least 3 months after prior whole brain radiotherapy and/or stereotactic radiosurgery AND do not require steroids are eligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed, provided the hemoglobin level has not decreased ≥ 1 g/dL within 1 week)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia, including LOWN IV arrhythmia (defined as 2 or more consecutive ventricular premature complexes)
• No advanced coronary artery disease
• No New York Heart Association class III or IV cardiac disease

Other

• No prior wound-healing disorders
• No peptic ulcer disease within the past 6 months
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

• No other malignancy within the past 5 years except for the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • Carcinoma in situ of the cervix
  • Adequately treated stage I or II cancer currently in complete remission
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior interferon alfa in the adjuvant setting for resected stage III melanoma allowed
• No prior endostatin, angiostatin, bevacizumab or any integrin-targeted drugs

• No more than 1 prior systemic biotherapy or biochemotherapy regimen for stage IV disease

  • Active vaccine therapy is not considered prior systemic therapy

Chemotherapy

• See Biologic therapy
• No more than 1 prior systemic chemotherapy regimen for stage IV disease
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics

Other

• Prior embolization or perfusion allowed provided there is objective evidence of disease progression for response assessment

• No concurrent anticoagulant therapy (e.g., warfarin, heparin, or hirudin derivatives)

  • Concurrent low molecular weight heparin or other low-dose anticoagulants for flushing IV port devices or for thrombosis prophylaxis allowed
• No other concurrent anticancer therapy
• No other concurrent investigational agents