Clinical trial NCT01259089 (phase 1/phase 2, status: completed)
Conditions: adenocarcinoma of the lung, non-small cell lung cancer
ICD codes: D02.20, D02.21, D02.22, C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: erlotinib hydrochloride, hsp90 inhibitor auy922
SMILES: COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2, CCNC(=O)C1=NOC(=C1C1=CC=C(CN2CCOCC2)C=C1)C1=CC(=C(O)C=C1O)C(C)(C)C
Eligibility criteria:

        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)