AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed recurrent or metastatic malignant melanoma (stage IV acral lentiginous, lentigo maligna, superficial spreading or ocular malignant melanoma)

• Patients must have measurable disease, 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

  • Previously irradiated lesions are not considered measurable, unless they have demonstrated progression prior to study entry

• Patients must not have had any prior chemotherapy (including regional therapy); prior adjuvant immunotherapy is permitted if completed > 3 months prior to study entry; patients may have received prior radiation therapy, if completed >= 4 weeks prior to study entry

  • Previous surgery is permissible, if performed >= 4 weeks prior to study entry
• Life expectancy of greater than 12 weeks
• ECOG performance status =< 2 (Karnofsky >= 60%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL
• Total bilirubin < 1.5 x institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal (5 x ULN if liver metastases)
• Creatinine within institutional normal limits
• Creatinine within institutional normal limits OR
• Creatinine clearance >= 60 mL/min/m^2 for patients with creatinine levels above institutional normal
• Baseline blood pressure must be < 140/90mmHg; patients may be taking antihypertensive medications
• AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had any previous chemotherapy, or immunotherapy for recurrent/metastatic disease; patients who have had radiotherapy or major surgery within 4 weeks prior to entering the study or those who have not recovered from adverse events due to treatment received more than 4 weeks earlier
• Patients may not be concurrently receiving any other investigational agents nor have participated in an investigational trial of bio-, chemo- or immunotherapy agents
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
• Mean QTc > 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
• Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
• Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; breastfeeding should be discontinued if the mother is treated with AZD2171
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Any significant abnormality noted in the ECG within 14 days of treatment
• A New York Heart Association classification of III or IV (NOTE: Patients classified as class II controlled with treatment may continue with increase monitoring)
• Conditions requiring concurrent use of drugs or biologics with proarrhythmic potential; these drugs are prohibited during studies with AZD2171