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

Purpose

The purpose of this study is to determine if AUY922 has superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor have EGFR mutations.

Condition	Intervention	Phase
Advanced Non Small Cell Lung Cancer (NSCLC)	Drug: AUY922 Drug: Docetaxel Drug: Pemetrexed	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

Drug Information available for: Docetaxel Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression Free Survival (PFS) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
To compare PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. PFS will be based on local investigator assessment per RECIST 1.1

Secondary Outcome Measures:

Overall Survival (OS) [ Time Frame: from randomization until death up to death ] [ Designated as safety issue: No ]
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 will be censored at the last known date patient was alive.
Overall Response Rate (ORR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
ORR will be compared between treatment arms. The ORR will be based on local investigator assessment per RECIST 1.1
Disease Control Rate (DCR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
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) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
TTR will be compared between treatment arms. The TTR will be based on local investigator assessment per RECIST 1.1
Duration of Response (DOR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
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) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
Rate of serious Aadverse events (SAEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
Change in laboratory paramenters [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.
Time to Progression (TTP) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1


Enrollment:	56
Study Start Date:	November 2012
Study Completion Date:	November 2015
Primary Completion Date:	November 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AUY922 arm AUY922 will be administered weekly	Drug: AUY922 AUY922 will be given 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 docetaxel or pemetrexed will be given once every three weeks	Drug: Docetaxel Docetaxel will be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity Other Name: TAXOTERE Drug: Pemetrexed Pemetrexed will be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity Other Name: ALIMTA

Detailed Description:

The primary purpose of this study is 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 harbor EGFR activating mutations, and have developed resistance to EGFR TKI.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646125

Show 27 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01646125 History of Changes
Other Study ID Numbers:	CAUY922A2207 2012-001050-25
Study First Received:	June 26, 2012
Last Updated:	December 16, 2015
Health Authority:	United States: Food and Drug Administration Australia: National Health and Medical Research Council France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Hong Kong: Department of Health Norway: Norwegian Medicines Agency Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Netherlands: Dutch Health Care Inspectorate Netherlands: Medical Ethics Review Committee (METC) United Kingdom: Medicines and Healthcare Products Regulatory Agency Spain: Spanish Agency of Medicines South Korea: Korea Food and Drug Administration (KFDA) Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Korea: Food and Drug Administration

Keywords provided by Novartis:


HSP90, AUY922, Pemetrexed, Docetaxel, EGFR TKI, EGFR mutations, NSCLC, non small cell lung cancer

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

ClinicalTrials.gov processed this record on September 23, 2016