Inclusion Criteria

- Histologically confirmed unresectable stage III or stage IV melanoma

- Treatment of unresectable stage III or stage IV melanoma with a tyrosine kinase
inhibitor within prior 4 months. Sorafenib for purposes of eligibility will not be
considered acceptable prior therapy

- Sufficient tumor available to determine if expresses wild-type or mutated BRAF if
result not already known. The presence or absence of BRAF mutation needs to be
determined at BWH, MGH, BIDMC, by Drs. Christopher Corless and Michael Heinrich at
Cancer Pathology Shared Resource Oregon Health & Science University, or in context of
eligibility assessment after signing consent to a previous clinical trial

- Sufficient tumor available to determine if expresses a mutation KIT

- Agreement to allow tumor to be evaluated for mutations in KIT and BRAF

- ECOG performance status ≤ 1

- Life expectancy of ≥ 6 months

- Age ≥ 18 years

- WBC ≥ 3 x 103/ul

- ANC ≥ 1,500/ul

- Platelets ≥ 100 x 103/ul

- Hemoglobin ≥ 9 gm/dl

- Serum creatinine ≤ 1.5 x ULN

- Calculated creatinine clearance ≥ 60 mL/min

- AST ≤ 2.5 x ULN; -OR- AST ≤ 5 x ULN in the presence of known liver metastases

- ALT ≤ 2.5 x ULN; -OR- ALT ≤ 5 x ULN in the presence of known liver metastases

- Total bilirubin ≤ 1.5 x ULN

- Potassium within normal range or correctable with supplements

- Magnesium within normal range or correctable with supplements

- Corrected serum calcium within normal range, or correctable with supplements

- Not pregnant or breastfeeding. Female subjects of childbearing age must have a
negative serumpregnancy test at study entry

- Women of childbearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation and for 6 months
following last study drug administration

- Agreement to provide blood samples for pharmacodynamic studies utilizing Peripheral
Blood Mononuclear Cells (PMBCs) as outlined in protocol

- At least one site of measurable disease as defined by at least 1 cm in greatest
dimension. This site must be different from the sites to be used for biopsy. No prior
radiation therapy or directed ablation to the site of measureable disease

- Able to understand and willing to sign a written informed consent document

- Willing and able to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures

- No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to
study entry

- No radiotherapy within 4 weeks prior to study entry

- Subject has recovered from adverse events due to agents administered more than 4
weeks earlier

- No tyrosine kinase inhibitor within 14 days prior to study entry

- No major surgery within 4 weeks prior to first dose of STA-9090

- No minor surgery within 7 days of first dose of STA-9090

- No history of or current coronary artery disease, myocardial infarction, angina
pectoris, angioplasty

- or coronary bypass surgery

- No current treatment with the following antiarrythmic drugs: flecainide, moricizine
or propafenone

- No NYHA class II/III/IV congestive heart failure with a history of dyspnea,
orthopnea, or edema that requires current treatment with angiotensin convering enzyme
inhibitors, angiotensin II receptor blockers, beta-blockers, or diuretics

- No current or prior radiation to the left hemithorax

- No embolization procedure or ablation procedure to treat tumor within 4 weeks of
first dose of STA- 9090

- Not receiving any other investigational agents

- No poor venous access for study drug administration unless subject can use silicone
based catheters

- No history of brain metastases or of leptomeningeal involvement

- No history of severe allergic reactions or hypersensitivity reactions attributed to
compounds of similar chemical or biologic composition to STA-9090 (e.g. olyethylene
glycol [PEG] 300 or Polysorbate 80)

- Baseline QTc ≤ 470 msec

- No previous history of QT prolongation while taking other medications

- Ventricular ejection fraction (EF) > 55%

- No treatment with chronic immunosuppressants

- No melanoma of ocular primary

- No prior treatment with hsp90 inhibitor

- No uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, ventricular arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- No other medications, or severe acute/chronic medical of psychiatric conditions or
laboratory abnormality that may increase the risk associated with the study
participation or study drug administration, or may interfere with the interpretation
of study results, and in the judgment of the investigator would make the subject
inappropriate for entry into the study

- No history of a different malignancy except for the following circumstances.
Individuals with a history of other malignancies are eligible if they have been
disease-free for at least 5 years and are deemed by the investigator to be at low
risk for recurrence of that malignancy. Individuals with the following cancers are
eligible if diagnosed and treated within the past 5 years: cervical cancer in situ,
and basal cell or squamous cell carcinoma of the skin

- No HIV-positive subject on combination antiretroviral therapy

- No more than 3 prior systemic therapies for unresectable stage III or stage IV
melanoma

- No concomitant use of medications associated with a high incidence of QT prolongation
as outlined