An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01646125
First received: June 26, 2012
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to determine if AUY922 has superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor have EGFR mutations.


Condition Intervention Phase
Advanced Non Small Cell Lung Cancer (NSCLC)
Drug: AUY922
Drug: Docetaxel
Drug: Pemetrexed
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
    To compare PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. PFS will be based on local investigator assessment per RECIST 1.1


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: from randomization until death up to death ] [ Designated as safety issue: No ]
    OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS will be censored at the last known date patient was alive.

  • Overall Response Rate (ORR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
    ORR will be compared between treatment arms. The ORR will be based on local investigator assessment per RECIST 1.1

  • Disease Control Rate (DCR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
    Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1

  • Time to Response (TRR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
    TTR will be compared between treatment arms. The TTR will be based on local investigator assessment per RECIST 1.1

  • Duration of Response (DOR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
    The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1

  • Rate of Adverse Events (AEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
    To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.

  • Rate of serious Adverse events (SAEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
    To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.

  • Change in laboratory parameters [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
    Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

  • Time to Progression (TTP) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
    TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1


Estimated Enrollment: 108
Study Start Date: November 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AUY922 arm
AUY922 will be administered weekly
Drug: AUY922
AUY922 will be given i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment
Active Comparator: chemotherapy arm
docetaxel or pemetrexed will be given once every three weeks
Drug: Docetaxel
Docetaxel will be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity
Other Name: TAXOTERE
Drug: Pemetrexed
Pemetrexed will be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity
Other Name: ALIMTA

Detailed Description:

The primary purpose of this study is to compare the efficacy of AUY922, when administered i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients with advanced NSCLC, whose tumors harbor EGFR activating mutations, and have developed resistance to EGFR TKI.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically or cytologically documented, locally advanced (stage IIIB who are not amenable to combined modality treatment) or recurrent or metastatic (Stage IV) non-small cell lung cancer.
  2. Patients must have EGFR gene mutation in their tumors. This can be source - documented by one of the following:

    • Provide a pathology report that indicates the patient's tumor had EGFR activating mutation in the past.

    Or:

    • Perform testing (local or central) in an archival tumor or a fresh baseline biopsy tumor tissue to show the presence of EGFR activating mutation.

  3. Patients must have documented clinical benefit (CR, PR, or patients with SD for 6 months or greater) on prior EGFR TKI (e.g. erlotinib or gefitinib) followed by documented progression according to RECIST.
  4. Patients must have received prior platinum containing treatment.
  5. WHO performance status of 0-1

Exclusion Criteria:

  1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease. Chemotherapy administered as neoadjuvant or adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.
  2. Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation
  3. Prior treatment with an HSP90 inhibitor

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT01646125

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Hide Study Locations
Locations
United States, California
Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr. Recruiting
Los Angeles, California, United States, 90048
Contact: Hannah Tualla    310-423-2276    Virginia.naaessig@cshs.org   
Principal Investigator: Ronald B. Natale         
University of California at Los Angeles David Geffen School - UCLA Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Julie Rothermich    310-586-2098    jrothermich@mednet.ucla.edu   
Principal Investigator: Edward Garon         
UC Davis Comprehensive Cancer Center Withdrawn
Sacramento, California, United States, 95817
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute AUY922A2207 Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Diana S. Lima    813-745-6895    diana.lima@moffitt.org   
Principal Investigator: Jhanelle Gray         
United States, Kentucky
Norton Cancer Institute Clinical Research Program Recruiting
Louisville, Kentucky, United States, 40202
Contact: Lauren Zutt       lauren.zutt@nortonhealthcare.org   
Principal Investigator: John T. Hamm         
United States, Maryland
Associates in Oncology/Hematology, P.C. SC Recruiting
Rockville, Maryland, United States, 20850
Contact: Jason Thayer       jthayer@aohmd.com   
Principal Investigator: Paul Thambi         
United States, Massachusetts
Dana Farber Cancer Institute DFCI AUY Withdrawn
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University School of Medicine Wash.Univ. School of Medicine Recruiting
St Louis, Missouri, United States, 63110
Contact: Melissa Haley    314-286-2694    mhaley@dom.wustl.edu   
Principal Investigator: Saiama Waqar         
United States, New York
NYU Langone Arena Oncology SC Location Not yet recruiting
Lake Success, New York, United States, 11042
Contact: Victoria Maresca-Travers    516-466-6611 ext 121    vtravers@researchcra.com   
Principal Investigator: Nikhal Uppal         
United States, North Carolina
Duke University Medical Center Morris Building Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Melody Torain    +1 919 681 6932    melody.torain@dm.duke.edu   
Principal Investigator: Frank Russell Dunphy         
United States, South Carolina
Medical University of South Carolina AUY922A2207 Not yet recruiting
Charleston, South Carolina, United States, 29425
Contact: Delia Short    843-792-6429    shortd@musc.edu   
Principal Investigator: Keisuke Shirai         
United States, Wisconsin
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5 Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Denae Walters    608-262-8126    dmwalters@uwcarbone.wisc.edu   
Principal Investigator: Anne M. Traynor         
Australia, Victoria
Novartis Investigative Site Withdrawn
Geelong, Victoria, Australia, 3220
Novartis Investigative Site Withdrawn
Heidelberg, Victoria, Australia, 3084
Novartis Investigative Site Withdrawn
Wodonga, Victoria, Australia, 3690
France
Novartis Investigative Site Recruiting
Creteil, France, 94000
Novartis Investigative Site Recruiting
Marseille cedex 20, France, 13915
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Hong Kong
Novartis Investigative Site Not yet recruiting
Hong Kong, Hong Kong
Novartis Investigative Site Recruiting
Hong Kong, Hong Kong
Italy
Novartis Investigative Site Recruiting
Monza, MB, Italy, 20900
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Novartis Investigative Site Recruiting
Parma, PR, Italy, 43100
Novartis Investigative Site Recruiting
Orbassano, TO, Italy, 10043
Novartis Investigative Site Recruiting
Udine, UD, Italy, 33100
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 464-8681
Novartis Investigative Site Recruiting
Hirakata-city, Osaka, Japan, 573-1191
Novartis Investigative Site Recruiting
Koto, Tokyo, Japan, 135-8550
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 738-736
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 137-701
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site Recruiting
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site Not yet recruiting
Maastricht, Netherlands, 6229 HX
Norway
Novartis Investigative Site Recruiting
Bergen, Norway, -N5021
Novartis Investigative Site Recruiting
Oslo, Norway, NO-0379
Novartis Investigative Site Withdrawn
Trondheim, Norway, 7006
Poland
Novartis Investigative Site Withdrawn
Otwock, Mazowieckie, Poland, 05-400
Novartis Investigative Site Recruiting
Gdansk, Poland, 80-952
Novartis Investigative Site Not yet recruiting
Szczecin, Poland, 70-891
Novartis Investigative Site Not yet recruiting
Warszawa, Poland, 02-781
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28040
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Taiwan
Novartis Investigative Site Active, not recruiting
Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan, 33305
Novartis Investigative Site Recruiting
Taichung, Taiwan, 407
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10048
United Kingdom
Novartis Investigative Site Not yet recruiting
Maidstone, Kent, United Kingdom, M16 9QQ
Novartis Investigative Site Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Novartis Investigative Site Recruiting
Leicester, United Kingdom, LE1 5WW
Novartis Investigative Site Not yet recruiting
Manchester, United Kingdom, M20 2BX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01646125     History of Changes
Other Study ID Numbers: CAUY922A2207, 2012-001050-25
Study First Received: June 26, 2012
Last Updated: March 14, 2014
Health Authority: United States: Food and Drug Administration
Australia: National Health and Medical Research Council
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hong Kong: Department of Health
Norway: Norwegian Medicines Agency
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
South Korea: Korea Food and Drug Administration (KFDA)
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Korea: Food and Drug Administration

Keywords provided by Novartis:
HSP90, AUY922, Pemetrexed, Docetaxel, EGFR TKI, EGFR mutations, NSCLC, non small cell lung cancer

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
Docetaxel
Pemetrexed
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 01, 2014