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A Phase I/II Trial of Hsp 90 Inhibitor AUY-922 in Patients With Lung Adenocarcinoma With "Acquired Resistance" to EGFR Tyrosine Kinase Inhibitors

Phase 1/Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Lung, Non-small Cell Lung Cancer

Thank you

Trial Information

A Phase I/II Trial of Hsp 90 Inhibitor AUY-922 in Patients With Lung Adenocarcinoma With "Acquired Resistance" to EGFR Tyrosine Kinase Inhibitors

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

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

- 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

- 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)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximally tolerated dose (MTD) of AUY922 (Phase I)

Outcome Description:

To determine the maximally tolerated dose (MTD), and recommended phase II dose of AUY922 when given in combination with erlotinib for patients with acquired resistance to erlotinib. (Phase I)

Outcome Time Frame:

At weeks 1-4 and every 2 weeks thereafter

Safety Issue:


Principal Investigator

Melissa Johnson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Food and Drug Administration

Study ID:

NU 10L01



Start Date:

March 2011

Completion Date:

December 2015

Related Keywords:

  • Adenocarcinoma of the Lung
  • Non-Small Cell Lung Cancer
  • Adenocarcinoma of the Lung
  • Non-small Cell Lung Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Northwestern University Chicago, Illinois  60611