hsp90 inhibitor auy922 and erlotinib hydrochloride in treating patients with stage iiib-iv non-small cell lung cancer

Conditions: Adenocarcinoma of the Lung; Non-small Cell Lung Cancer

Summary: hsp90 inhibitor auy922 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. this phase i/ii trial is studying the side effects and best dose of hsp90 inhibitor auy922 when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage iiib-iv non-small cell lung cancer.

this is a phase i, dose-escalation study of hsp90 inhibitor auy922 followed by a phase ii study. patients receive hsp90 inhibitor auy922 iv over 1 hour once weekly and oral erlotinib hydrochloride once daily. courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up periodically.

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 * 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 =\ = 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)

Keywords: adenocarcinoma of the lung non-small cell lung cancer