Phase 2 Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Lecia V. Sequist, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01854034
First received: May 12, 2013
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: AUY922
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Overall Response Rate to AUY922 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the overall response rate to AUY922 in patients with advanced NSCLC exon 20 insertion mutations in EGFR


Secondary Outcome Measures:
  • Estimate Progression Free and Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To estimate progression-free survival (PFS) and overall survival (OS) in the study population

  • Determine safety and tolerability of AUY922 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the safety and tolerability of AUY922

  • Explore variance in clinical outcome between different mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To explore variance in clinical outcome between different types of exon 20 EGFR mutations


Estimated Enrollment: 29
Study Start Date: July 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AUY922 Treatment Arm
AUY922 administered once weekly via intravenous, 70 mg/m2
Drug: AUY922
AUY922 administered intravenously once a week at 70mg/m2

Detailed Description:

Interested patients will be asked to undergo some screening tests and procedures to confirm that they are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that patients do not take part in the research study. If patients have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history physical exam, performance status, assessment of tumor, EKG, electrocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine test and collection of a piece of the stored tumor tissue.

The study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. Patients will receive an infusion of AUY922 on days 1, 8 and 15 of each cycle (once per week). The infusion will take about 60 minutes.

A schedule of clinic visits for the study is summarized below.

Cycle 1, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; routine urine test Cycle 1, Day 2: EKG Cycle 1, Day 3: EKG Cycle 1, Day 8: Vital signs, performance status, EKG, questions about side effects and other medications taken Cycle 1, Day 15: Physical exam, including measurement of vital signs, performance status; EKG; blood draw; questions about side effects and other medications taken Note that in Cycle 1 patients will need to stay at (or return to) the clinic for the last EKG following the Day 1 AUY922 infusion, and come to the clinic on Days 2 and 3 for EKGs.

Cycle 2 and beyond, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; questions about side effects and other medications taken; routine urine test Cycle 2 and beyond, Day 8: Vital signs; performance status; EKG; questions about side effects and other medications taken Cycle 2 and beyond, Day 15: Physical exam, including measurement of vital signs; performance status; EKG; blood draw; questions about side effects and other medications taken.

Additional EKGs may be done at any time if the study doctor thinks it is necessary. A blood test to measure the amount of cardiac enzymes in the blood may be done whenever abnormal findings are suspected or seen on the EKG.

Additional tests and procedures:

  • CT or MRI scans will be done to measure the disease about every 6 weeks.
  • A blood pregnancy test, for women who can become pregnant, will be performed every 6 weeks or at any point in which pregnancy is suspected.
  • A standard eye exam will be done on Cycle 3, Day 1. Additional eye exams will be done if patients experience any eye-related symptoms, such as changes in vision.

Within 1 week after the last dose of the study drug AUY922, patients will be asked to return to the clinic. At this visit the following will be done: physical examination, performance status, EKG, ECHO or MUGA scan, blood draw, urine test, eye exam, questions about side effects and other medications taken. Patients will be asked to return to the clinic a second time so investigators can follow-up on any ongoing side effects after stopping AUY922.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01854034

Contacts
Contact: Lecia Sequist, MD, MPH 6177244000 lvsequist@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lecia Sequist, MD, MPH    617-724-4000    lvsequist@partners.org   
Principal Investigator: Lecia Sequist, MD, MPH         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Leena Gandhi, MD, PhD    617-632-6049    lgandhi@partners.org   
Principal Investigator: Leena Gandhi, MD, PhD         
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Leena Gandhi, MD, PhD    617-632-6049    lgandhi@partners.org   
Principal Investigator: Leena Gandhi, MD, PhD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Daniel Costa, MD    617-667-9236    dbcosta@bidmc.harvard.edu   
Principal Investigator: Daniel Costa, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Lecia Sequist, MD, MPH Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Lecia V. Sequist, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01854034     History of Changes
Other Study ID Numbers: 12-484
Study First Received: May 12, 2013
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Advanced disease
EGFR mutation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 26, 2014