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

Phase 2TerminatedNCT01646125

Novartis Pharmaceuticals59 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Non Small Cell Lung Cancer (NSCLC)

Interventions

AUY922

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (27)

Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.

Los Angeles, California, United States

Maryland Oncology Hematology, P.A. SC

Rockville, Maryland, United States

University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5

Madison, Wisconsin, United States

Novartis Investigative Site

Marseille, Bouches Du Rhone, France

Novartis Investigative Site

Créteil, France

Novartis Investigative Site

Villejuif, France

Novartis Investigative Site

Hong Kong, Hong Kong

Novartis Investigative Site

Monza, MB, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Parma, PR, Italy

...and 17 more locations

Outcomes

Primary Outcomes

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

Time frame: 16 months

Secondary Outcomes

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.

Time frame: 16 months

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.

Time frame: from randomization until death up to death

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