Status:
COMPLETED
Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer
Lead Sponsor:
Northwestern University
Collaborating Sponsors:
Robert H. Lurie Cancer Center
Conditions:
Adenocarcinoma of the Lung
Non-small Cell Lung Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief 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 bes...
Detailed Description
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 onc...
Eligibility Criteria
Inclusion
- 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
- 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)
Key Trial Info
Start Date :
April 27 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 29 2014
Estimated Enrollment :
38 Patients enrolled
Trial Details
Trial ID
NCT01259089
Start Date
April 27 2011
End Date
September 29 2014
Last Update
September 11 2019
Active Locations (2)
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1
Northwestern University
Chicago, Illinois, United States, 60611
2
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065