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 ago) and women < 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for > 24 months
Total bilirubin =< 1.5 x Upper Limit of Normal (ULN)
AST/SGOT and ALT/SGPT =< 3.0 x ULN, or =< 5.0 x ULN if liver metastasis present
Absolute neutrophil count (ANC) >= 1.5 x10^9/L
Hemoglobin (Hgb) >= 9g/dL
Platelets (plts) >= 100 x 10^9/L
Serum creatinine =< 1.5 x ULN or 24 hour clearance >= 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 =< 2 weeks prior to randomization or who have not recovered from such therapy
History (or family history) of long QT syndrome
Mean QTc >= 450 msec on baseline ECG
History of clinically manifested ischemic heart disease =< 6 months prior to study start
History of heart failure or left ventricular (LV) dysfunction (LVEF =< 45%) by MUGA or ECG
Clinically significant resting bradycardia (< 50 beats per minute)
Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemi-block (LAHB); ST segment elevation or depression > 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)