Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

Inclusion Criteria

• All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q)
• Radiographic progression by RECIST during treatment with erlotinib/gefitinib
• Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time
• Measurable (RECIST) indicator lesion not previously irradiated
• Must have undergone a biopsy after the development of acquired resistance
• Karnofsky Performance Status >= 70% OR ECOG/WHO Performance Status 0-1
• Signed informed consent
• Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period = 24 months
• Total bilirubin = = 1.5 x10^9/L
• Hemoglobin (Hgb) >= 9g/dL
• Platelets (plts) >= 100 x 10^9/L
• Serum creatinine = = 50 mL/min

Exclusion Criteria

• Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids
• Prior treatment with any HSP90 inhibitor compounds
• Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed)
• Palliative radiation within 2 weeks
• Unresolved diarrhea >= CTCAE grade 2
• Pregnant or lactating women
• Women of childbearing potential (WCBP) (i.e. women able to become pregnant) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile); male patients whose partners are WCBP not using double-barrier methods of contraception
• Acute or chronic liver or renal disease
• Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
• Major surgery = = 450 msec on baseline ECG
• History of clinically manifested ischemic heart disease = 1mm, or 2nd (Mobitz II), or 3rd degree AV block
• History ventricular tachycardia
• Other clinically significant heart disease including congestive heart failure (New York Heart Association class III/IV) or uncontrolled hypertension (> 160/90 despite intensive medical management)
• Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval and cannot be switched or discontinued to an alternative drug prior to commencing AUY922
• Known diagnosis of HIV infection (HIV testing is not mandatory)
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
• Patients who are receiving warfarin (Coumadin®) will be excluded unless =< 2 mg/d, with an INR < 1.5
• Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)