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

• ClinicalTrials.gov Identifier: NCT01646125
• Recruitment Status: Terminated
• First Posted: July 20, 2012
• Results First Posted: March 13, 2017
• Last Update Posted: July 24, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease	Intervention/treatment	Phase
Advanced Non Small Cell Lung Cancer (NSCLC)	Drug: AUY922; Drug: Docetaxel; Drug: Pemetrexed	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 23, 2012
• Actual Primary Completion Date: November 4, 2015
• Actual Study Completion Date: November 4, 2015

Arms and Interventions

Arm	Intervention/treatment
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.	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.
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.	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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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
4. 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
5. 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
6. 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.
7. 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.
8. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

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

Los Angeles, California, United States, 90048

United States, Maryland

Maryland Oncology Hematology, P.A. SC

Rockville, Maryland, United States, 20850

United States, Wisconsin

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

Madison, Wisconsin, United States, 53792-6164

France

Novartis Investigative Site

Marseille cedex 20, Bouches Du Rhone, France, 13915

Novartis Investigative Site

Creteil, France, 94000

Novartis Investigative Site

Villejuif Cedex, France, 94805

Hong Kong

Novartis Investigative Site

Hong Kong, Hong Kong

Italy

Novartis Investigative Site

Monza, MB, Italy, 20900

Novartis Investigative Site

Milano, MI, Italy, 20133

Novartis Investigative Site

Parma, PR, Italy, 43100

Novartis Investigative Site

Orbassano, TO, Italy, 10043

Japan

Novartis Investigative Site

Koto ku, Tokyo, Japan, 135 8550

Korea, Republic of

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 05505

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 06351

Novartis Investigative Site

Seoul, Seocho Gu, Korea, Republic of, 06591

Novartis Investigative Site

Seoul, Korea, Republic of, 03722

Netherlands

Novartis Investigative Site

Amsterdam, Netherlands, 1081 HV

Novartis Investigative Site

Groningen, Netherlands, 9713 GZ

Norway

Novartis Investigative Site

Bergen, Norway, 5021

Novartis Investigative Site

Oslo, Norway, NO-0424

Poland

Novartis Investigative Site

Gdansk, Poland, 80 952

Spain

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Madrid, Spain, 28034

Taiwan

Novartis Investigative Site

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

Novartis Investigative Site

Taichung, Taiwan, 407

Novartis Investigative Site

Taipei, Taiwan, 10048

United Kingdom

Novartis Investigative Site

Leicester, United Kingdom, LE1 5WW

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01646125
• Other Study ID Numbers: CAUY922A2207; 2012-001050-25 ( EudraCT Number )
• First Posted: July 20, 2012
• Results First Posted: March 13, 2017
• Last Update Posted: July 24, 2019
• Last Verified: July 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Docetaxel; Pemetrexed; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors