Phase 2 Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
Condition: Non Small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: AUY922
Intervention description: AUY922 administered intravenously once a week at 70mg/m2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced disease; EGFR mutation

Summary:

      This research study is a Phase II clinical trial, which tests the safety and effectiveness of
      an investigational drug to learn whether the drug works in treating a specific cancer.
      "Investigational" means that the drug is being studied. It also means that the FDA has not
      yet approved the drug for your type of cancer or for any use outside of research studies.

      It has been found that some people with NSCLC have a change (mutation) in a certain gene
      called the EGFR gene. This mutated gene helps cancer cells grow. The majority of NSCLC
      patients with EGFR mutations achieve good outcomes with erlotinib or other EGFR inhibitor
      therapies, with a high response rate, prolonged progression-free survival and possibly
      improved overall survival from therapy. However, the 4% of EGFR mutant patients that harbor
      an exon 20 insertion mutation historically have reaped little benefit from EGFR-directed
      therapy due to the low affinity of this mutation for direct EGFR inhibitors, especially
      erlotinib and gefitinib (see Yasuda et al, Lancet Oncol 2011). This group of patients is
      ideal for studying other targeted therapeutic strategies that could affect the oncogene
      mutation in EGFR via alternative mechanisms.

      AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This
      drug has been used in other research studies. Information from those other research studies
      suggests that AUY922 may be effective in killing cancer cells in patients with exon 20
      insertion mutations in EGFR.

      The purpose of this study is to test the safety of AUY922 and determine how well AUY922 works
      for participants with advanced NSCLC and exon 20 insertion mutations in EGFR.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed stage IV or recurrent NSCLC

          -  Measurable disease by RECIST 1.0

          -  Must have received at least one prior line of therapy for advanced lung cancer (no
             maximum number)

          -  Life expectancy of at least 12 weeks

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Radiation within 2 weeks

          -  Cytotoxic chemotherapy or monoclonal antibodies within 4 weeks

          -  EGFR tyrosine kinase inhibitor within 2 weeks

          -  Other small molecule inhibitor within 2 weeks

          -  Experimental treatment within 30 days

          -  Prior treatment with any HSP90 or HDAC inhibitor compound

          -  Known and untreated brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AUY922

          -  Unresolved diarrhea greater than or equal to CTCAE version 4, grade 1

          -  Major surgery within 2 weeks of starting study drug or have not recovered from side
             effects of surgery

          -  Known disorders due to a deficiency in bilirubin glucuronidation

          -  Requiring use of therapeutic doses of warfarin (Coumadin)

          -  History of long QT syndrome

          -  History of clinically manifest ischemic heart disease, heart failure or left
             ventricular dysfunction

          -  Clinically significant ECG abnormalities

          -  Other clinically significant heart disease

          -  Currently receiving treatment with any medication which has a relative risk of
             prolonging the QTc interval or inducing Torsades de Pointes

          -  On a cardiac pacemaker

          -  Concurrent malignancies or invasive cancers diagnosed within 3 years except for
             adequately treated basal cell cancer of the skin or in situ cancer of the cervix

          -  Known to be HIV positive