Brief Title
Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer
Official Title
A Phase I/II Trial of Hsp 90 Inhibitor AUY-922 in Patients With Lung Adenocarcinoma With "Acquired Resistance" to EGFR Tyrosine Kinase Inhibitors
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 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.
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 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I)
Secondary Outcome
Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II)
Condition
Adenocarcinoma of the Lung
Intervention
erlotinib hydrochloride
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
38
Start Date
April 27, 2011
Completion Date
September 29, 2014
Primary Completion Date
June 4, 2013
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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Melissa Johnson, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01259089
Organization ID
NU 10L01
Secondary IDs
STU00038215
Responsible Party
Sponsor
Study Sponsor
Northwestern University
Collaborators
Robert H. Lurie Cancer Center
Study Sponsor
Melissa Johnson, Principal Investigator, Northwestern University
Verification Date
October 2018