STA-9090(Ganetespib) in Patients With Unresectable Stage III or Stage IV Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: STA-9090
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage III; Stage IV; Unresectable; Metastatic

Summary:

      STA9090 is a drug which inactivates or blocks the work of a protein called Heat Shock Protein
      90 or HSP90. HSP90 is a protein that helps some molecules inside your cells to have the right
      shape. By stopping HSP90's activity, those molecules never get to have the right structure of
      be functional and they are destroyed. The investigators believe that if they stop the
      activity of HSP90, the rapidly dividing cells that are in your tumor(s) may slow down. In
      this research study the investigators are looking to see how well STA9090 works in stopping
      the spread of your melanoma.
    

Eligibility 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