A Phase II Study to Evaluate the Efficacy and Safety of PTK787 in Patients With Metastatic Cutaneous Melanoma
A Phase II Study to Evaluate the Efficacy and Safety of PTK787 in Patients With Metastatic Cutaneous Melanoma
RATIONALE: Vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well vatalanib works in treating patients with metastatic cutaneous melanoma that cannot be removed by surgery.
OBJECTIVES:
Primary
Secondary
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
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:
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:
PRIOR CONCURRENT THERAPY:
Recovered from all prior therapy
Prior adjuvant therapy allowed
Prior radiotherapy allowed
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 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