Back to resultsAn Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations
Primary Purpose
Advanced Non Small Cell Lung Cancer (NSCLC)
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AUY922
Docetaxel
Pemetrexed
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Non Small Cell Lung Cancer (NSCLC) focused on measuring Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma, Squamous cell lung carcinoma, Large-cell lung carcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer, NSCLC, Large cell lung carcinoma, Large cell lung cancer, HSP90, AUY922, Pemetrexed, Docetaxel, EGFR TKI, EGFR mutations
Eligibility Criteria
Inclusion Criteria:
- 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.
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.
- 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.
- Patients must have received prior platinum containing treatment.
- WHO performance status of 0-1
Exclusion Criteria:
- 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.
- 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
- Prior treatment with an HSP90 inhibitor
Sites / Locations
- Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
- Maryland Oncology Hematology, P.A. SC
- University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
AUY922 arm
chemotherapy arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
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
Secondary Outcome Measures
Overall Response Rate (ORR)
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)
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)
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)
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)
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)
To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
Change in Laboratory Paramenters
Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.
Time to Progression (TTP)
TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01646125
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
An interim analysis was conducted in May-2014. Upon review of the data, the committee recommended study termination due to futility.
Study Start Date
November 23, 2012 (Actual)
Primary Completion Date
November 4, 2015 (Actual)
Study Completion Date
November 4, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Non Small Cell Lung Cancer (NSCLC)
Keywords
Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma, Squamous cell lung carcinoma, Large-cell lung carcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer, NSCLC, Large cell lung carcinoma, Large cell lung cancer, HSP90, AUY922, Pemetrexed, Docetaxel, EGFR TKI, EGFR mutations
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AUY922 arm
Arm Type
Experimental
Arm Description
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.
Arm Title
chemotherapy arm
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AUY922
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
TAXOTERE
Intervention Description
Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
ALIMTA
Intervention Description
Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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
Time Frame
16 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
16 months
Title
Overall Survival (OS)
Description
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.
Time Frame
from randomization until death up to death
Title
Disease Control Rate (DCR)
Description
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 Frame
baseline, until disease progression up to 24 months
Title
Time to Response (TRR)
Description
TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1
Time Frame
baseline, until disease progression up to 24 months
Title
Duration of Response (DOR)
Description
The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1
Time Frame
baseline, until disease progression up to 24 months
Title
Rate of Adverse Events (AEs)
Description
To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
Time Frame
baseline, until disease progression up to 24 months
Title
Change in Laboratory Paramenters
Description
Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.
Time Frame
baseline, until disease progression up to 24 months
Title
Time to Progression (TTP)
Description
TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
Time Frame
baseline, until disease progression up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
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.
Patients must have received prior platinum containing treatment.
WHO performance status of 0-1
Exclusion Criteria:
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.
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
Prior treatment with an HSP90 inhibitor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Maryland Oncology Hematology, P.A. SC
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States
Facility Name
Novartis Investigative Site
City
Marseille cedex 20
State/Province
Bouches Du Rhone
ZIP/Postal Code
13915
Country
France
Facility Name
Novartis Investigative Site
City
Creteil
ZIP/Postal Code
94000
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Parma
State/Province
PR
ZIP/Postal Code
43100
Country
Italy
Facility Name
Novartis Investigative Site
City
Orbassano
State/Province
TO
ZIP/Postal Code
10043
Country
Italy
Facility Name
Novartis Investigative Site
City
Koto ku
State/Province
Tokyo
ZIP/Postal Code
135 8550
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Seocho Gu
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Novartis Investigative Site
City
Oslo
ZIP/Postal Code
NO-0424
Country
Norway
Facility Name
Novartis Investigative Site
City
Gdansk
ZIP/Postal Code
80 952
Country
Poland
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Kuei-Shan Chiang
State/Province
Taoyuan/ Taiwan ROC
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
407
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations
We'll reach out to this number within 24 hrs