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

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ClinicalTrials.gov Identifier: NCT01646125
Recruitment Status : Terminated (An interim analysis was conducted in May-2014. Upon review of the data, the committee recommended study termination due to futility.)
First Posted : July 20, 2012
Results First Posted : March 13, 2017
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 26, 2012
First Posted Date  ICMJE July 20, 2012
Results First Submitted Date  ICMJE November 3, 2016
Results First Posted Date  ICMJE March 13, 2017
Last Update Posted Date July 24, 2019
Actual Study Start Date  ICMJE November 23, 2012
Actual Primary Completion Date November 4, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
Progression Free Survival (PFS) [ Time Frame: 16 months ]
Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2012)
Progression Free Survival (PFS) [ Time Frame: up to 12 months ]
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
  • Overall Response Rate (ORR) [ Time Frame: 16 months ]
    ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time.
  • Overall Survival (OS) [ Time Frame: from randomization until death up to death ]
    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 was to be censored at the last known date patient was alive.
  • Disease Control Rate (DCR) [ Time Frame: baseline, until disease progression up to 24 months ]
    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 ]
    TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: baseline, until disease progression up to 24 months ]
    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 ]
    To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
  • Change in Laboratory Paramenters [ Time Frame: baseline, until disease progression up to 24 months ]
    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 ]
    TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
Original Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2012)
  • Overall Survival (OS) [ Time Frame: from randomization until death up to 24 months ]
    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 date of last contact.
  • Overall Response Rate (ORR) [ Time Frame: baseline, until disease progression up to 24 months ]
    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 ]
    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 Progression (TTP) [ Time Frame: baseline, until disease progression up to 24 months ]
    TTP will be compared between treatment arms. The TTP 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 ]
    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 ]
    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 ]
    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 ]
    Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations
Official Title  ICMJE 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
Brief Summary

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

The primary purpose of this study was 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 harbored EGFR activating mutations, and had developed resistance to EGFR TKI.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Non Small Cell Lung Cancer (NSCLC)
Intervention  ICMJE
  • Drug: AUY922
    AUY922 was to be given by i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment.
  • Drug: Docetaxel
    Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity
    Other Name: TAXOTERE
  • Drug: Pemetrexed
    Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity
    Other Name: ALIMTA
Study Arms  ICMJE
  • Experimental: AUY922 arm

    Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm.

    AUY922 was to be administered weekly.

    Intervention: Drug: AUY922
  • Active Comparator: chemotherapy arm

    Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm.

    Pemetrexed or docetaxel was to be was to be given once every three weeks.

    Interventions:
    • Drug: Docetaxel
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 11, 2019)
59
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2012)
120
Actual Study Completion Date  ICMJE November 4, 2015
Actual Primary Completion Date November 4, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT01646125
Other Study ID Numbers  ICMJE CAUY922A2207
2012-001050-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP