Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

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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