Vatalanib in Treating Patients With Metastatic Cutaneous Melanoma That Cannot be Removed by Surgery

OBJECTIVES:

Primary

• To determine the response rate in patients with unresectable metastatic cutaneous melanoma treated with vatalanib.

Secondary

• To determine the time to progression in these patients.
• To determine the 6-month and 1-year survival of these patients.
• To determine the overall survival of these patients.
• To determine the safety and toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral vatalanib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed at 8 weeks and then periodically thereafter.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic cutaneous melanoma

• Unresectable disease
• Measurable disease, defined as ≥ 1 bidimensionally measurable lesion by clinical or radiological techniques (i.e., chest x-ray, CT scan, or conventional MRI scan) using RECIST criteria
• No history or presence of CNS disease (i.e., primary brain tumor, malignant seizures, clinically symptomatic CNS metastases, or carcinomatous meningitis)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 x ULN (≤ 5 if liver metastases are present)
• Transaminases ≤ 3 x ULN (≤ 5 if liver metastases are present)
• Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min
• Total urinary protein ≤ 500 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No history of other malignant disease except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other serious or uncontrolled illness which, in the opinion of the investigator, precludes study entry
• No medical or psychiatric condition that precludes giving informed consent
• No history of renal disease (e.g., glomerulonephritis) or renal vascular disease
• No acute or chronic active liver disease (e.g., hepatitis or cirrhosis)
• No concurrent severe and/or uncontrolled medical conditions that would compromise participation in the study, including any of the following:

• Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction within the past 6 months
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes
• Active or uncontrolled infection
• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib including, but not limited to, any of the following conditions:

• Ulcerative disease
• Uncontrolled nausea
• Vomiting
• Diarrhea which might result in malabsorption
• Any known malabsorption syndrome
• Bowel obstruction
• Inability to swallow the capsules/tablets

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• Prior adjuvant therapy allowed
• Prior radiotherapy allowed

• Measurable target lesions must not have been irradiated
• No more than one line of prior systemic therapy for advanced melanoma
• More than 4 weeks since prior chemotherapy, immunotherapy, or investigational agent
• More than 2 weeks since prior surgery
• No concurrent warfarin or other similar oral anticoagulants that are metabolized by the cytochrome p450 system

• Concurrent heparin allowed
• Concurrent radiotherapy for symptomatic disease is allowed, provided the lesions being irradiated contribute ≤ 20% of the sum of the longest diameter for all target lesions being used to determine response