Clinical trial NCT01646125: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.


Eligibility 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 16 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 16 months
measure: Overall Survival (OS)
timeFrame: from randomization until death up to death
measure: Disease Control Rate (DCR)
timeFrame: baseline, until disease progression up to 24 months
measure: Time to Response (TRR)
timeFrame: baseline, until disease progression up to 24 months
measure: Duration of Response (DOR)
timeFrame: baseline, until disease progression up to 24 months
measure: Rate of Adverse Events (AEs)
timeFrame: baseline, until disease progression up to 24 months
measure: Change in Laboratory Paramenters
timeFrame: baseline, until disease progression up to 24 months
measure: Time to Progression (TTP)
timeFrame: baseline, until disease progression up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
state: California
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. SC
state: Maryland
city: Madison
country: United States
facility: University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5
state: Wisconsin
city: Marseille cedex 20
country: France
facility: Novartis Investigative Site
state: Bouches Du Rhone
city: Creteil
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Kuei-Shan Chiang
country: Taiwan
facility: Novartis Investigative Site
state: Taoyuan/ Taiwan ROC
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: