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

NCT01646125 | Terminated Phase 2 Results DMC

• 2 other identifiers: CAUY922A22072012-001050-25
• Study Type: interventional
• Target: 59
• Locations: 12 countries
• Sites: 27

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  16 months

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  16 months

• Overall Survival (OS)

  from randomization until death up to death

• Disease Control Rate (DCR)

  baseline, until disease progression up to 24 months

• Time to Response (TRR)

  baseline, until disease progression up to 24 months

• Duration of Response (DOR)

  baseline, until disease progression up to 24 months

Study Arms (2)

AUY922 arm

EXPERIMENTAL

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.

Drug: AUY922

chemotherapy arm

ACTIVE COMPARATOR

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.

Drug: Docetaxel; Drug: Pemetrexed

Interventions

AUY922 DRUG

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.

AUY922 arm

Docetaxel DRUG

Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity

Also known as: TAXOTERE

chemotherapy arm

Pemetrexed DRUG

Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity

Also known as: ALIMTA

chemotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (27)

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

Los Angeles, California, 90048, United States

Location

Maryland Oncology Hematology, P.A. SC

Rockville, Maryland, 20850, United States

Location

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

Madison, Wisconsin, 53792-6164, United States

Location

Novartis Investigative Site

Marseille, Bouches Du Rhone, 13915, France

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Parma, PR, 43100, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Bergen, 5021, Norway

Location

Novartis Investigative Site

Oslo, NO-0424, Norway

Location

Novartis Investigative Site

Gdansk, 80 952, Poland

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305, Taiwan

Location

Novartis Investigative Site

Taichung, 407, Taiwan

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; Docetaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results to terminate the study early due to futility, data was not collected for this assessment on many of the secondary endpoints.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: July 20, 2012
• Study Start: November 23, 2012
• Primary Completion: November 4, 2015
• Study Completion: November 4, 2015
• Last Updated: July 24, 2019
• Results First Posted: March 13, 2017

Record last verified: 2019-07

Locations

TW (3); NL (2); NO (2); JP (1); ES (2); PL (1); FR (3); IT (4); HK (1); US (3); KR (4); GB (1)