- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01124864
A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy.
February 2, 2016 updated by: Novartis Pharmaceuticals
A Phase II, Multi-center, Open-label Study of AUY922 Administered IV on a Once-weekly Schedule in Patients With Advanced Non-small-cell Lung Cancer Who Have Received at Least Two Lines of Prior Chemotherapy
This study will assess the efficacy of AUY922, when administered weekly at 70 mg/m2, in adult patients with advanced Non-small-cell Lung Cancer (NSCLC), who have received at least two prior lines of chemotherapy.
Patients will be retrospectively, and prospectively, stratified based on their molecular tumor etiology.
The following strata was assigned: Patients with Epidermal growth factor receptor (EGFR) activating mutations, Patients with Kirstin Raus sarcoma virus (KRAS) activating mutations, Patients with EML4-ALK (anaplastic lymphoma kinase) translocations and patients that were both EGFR and Kras wild type.
Study Overview
Study Type
Interventional
Enrollment (Actual)
153
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Novartis Investigative Site
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Creteil, France, 94000
- Novartis Investigative Site
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Marseille cedex 20, France, 13915
- Novartis Investigative Site
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Villejuif Cedex, France, 94805
- Novartis Investigative Site
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Berlin, Germany, 13125
- Novartis Investigative Site
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Oldenburg, Germany, 26121
- Novartis Investigative Site
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Korea
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Seoul, Korea, Korea, Republic of, 05505
- Novartis Investigative Site
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Seoul, Korea, Korea, Republic of, 06351
- Novartis Investigative Site
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Seoul, Korea, Korea, Republic of, 137-701
- Novartis Investigative Site
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Seoul, Korea, Korea, Republic of, 110 744
- Novartis Investigative Site
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Amsterdam, Netherlands, 1081 HV
- Novartis Investigative Site
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Groningen, Netherlands, 9713 GZ
- Novartis Investigative Site
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Oslo, Norway, NO-0379
- Novartis Investigative Site
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Singapore, Singapore, 119228
- Novartis Investigative Site
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Catalunya
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Badalona, Catalunya, Spain, 08916
- Novartis Investigative Site
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Izmir, Turkey, 35040
- Novartis Investigative Site
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California
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Los Angeles, California, United States, 90095
- University of California at Los Angeles UCLA - Santa Monica
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Maryland
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Rockville, Maryland, United States, 20850
- Maryland Oncology Hematology, P.A. Dept. of Assoc. Onc/Hem
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute DFCI
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Pennsylvania
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Bethlehem, Pennsylvania, United States
- St. Luke's Hospital and Health Network St Luke's
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with histologically or cytologically confirmed advanced (stage IIIB or stage IV) NSCLC who have received at least two prior lines of treatment. Patients who, in the investigators opinion, are deemed unsuitable for the standard 2nd line chemotherapy will be eligible for protocol participation. One of the prior lines must have included a platinum agent. Prior treatment with a platinum agent is not a requirement for EGFR mutant patients and patients with EML4-ALK translocations
- Patients enrolled to the fifth stratum, modified EGFR mutant, must have documented prior response to EGFR TKI as defined by CR, PR or SD for 6 months or greater unless patient has de novo resistance to EGFR TKI (e.g. exon 20 insertions.)
- All patients must have at least one measurable lesion as defined by RECIST criteria. Previously irradiated lesions are not measurable unless the lesion is new or has demonstrated clear progression after radiation
- World Health Organization (WHO) performance status ≤ 2. For patients enrolled to the fifth stratum, modified EGFR mutant, World Health Organization (WHO) performance status ≤ 1
- Patients enrolled to the fifth stratum, modified EGFR mutant, must be willing and suitable to undergo fresh baseline biopsy prior to study treatment (unless patient had recent biopsy after EGFR TKI progression that concluded resistance to EGFR TKI.)
Hematologic:
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
- Hemoglobin (Hgb) ≥ 9 g/dl.
- Platelets (plt) ≥ 100 x 109/L.
Biochemistry:
- Total calcium (corrected for serum albumin) within normal limits or correctable with supplements.
- Magnesium within lower normal limits or correctable with supplements.
Adequate liver function defined as:
- AST/SGOT and ALT/SGPT ≤ 3.0 x Upper limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastasis are present.
- Serum bilirubin ≤ 1.5 x ULN.
- Serum albumin > 2.5 g/dL.
- Serum creatinine ≤ 1.5 x ULN or 24 hour clearance ≥ 50 mL/min.
Exclusion Criteria:
- Patients who have received more than four lines of prior treatment. Exception: Patients enrolled to the fifth stratum, modified EGFR mutant, must not have received more than two prior lines of therapy. Chemotherapy administered as adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.
- Patients with a history of CNS metastasis. Note: Patients without clinical signs and symptoms of CNS involvement are not required to have MRI of the brain. Exception: Patients with treated brain metastases who are asymptomatic, who has discontinued corticosteroids, and who have been clinically stable for one month will be eligible for protocol participation. This exception is not valid for patients enrolled to the fifth stratum, modified EGFR mutant. These patients must not have CNS involvement.
- Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound.
Patients must not have received:
- any systemic anti-cancer treatment or radiotherapy within 4 weeks prior to first dose of study treatment and should have recovered to baseline or less than Grade 1 from toxicities of such therapy prior to the first dose of study treatment
- 2 weeks for palliative radiotherapy to bones, 6 weeks for nitrosoureas and mitomycin
- 4 weeks for monoclonal antibodies
- and ≤5 half-life of the agent or active metabolites [if any] for continuous systemic anti-cancer treatment or investigational
- Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline.
Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: EGFR mutant patients
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation).
Patients received AUY922 at 70 mg/m^2 weekly infusions.
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AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution.
AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
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EXPERIMENTAL: Kras mutant patients
Patients with KRAS mutant tumors.
Patients received AUY922 at 70 mg/m^2 weekly infusions.
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AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution.
AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
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EXPERIMENTAL: EGFR and Kras wild type patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum.
Patients received AUY922 at 70 mg/m^2 weekly infusions.
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AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution.
AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
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EXPERIMENTAL: Patients with EML4-ALK translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase.
ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung.
EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain.
Patients received AUY922 at 70 mg/m^2 weekly infusions.
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AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution.
AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
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EXPERIMENTAL: Modified EGFR mutant patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI.
Patients received AUY922 at 70 mg/m^2 weekly infusions.
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AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution.
AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Response Assessment by Study Stratum - Per Investigator Assessment
Time Frame: 18 weeks
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The primary endpoint of the study was the investigator assessment of efficacy at 18 weeks in terms of response complete response (CR)/partial response (PR), stable disease (SD), or non clinical benefit (NCB) as assessed by response evaluation criteriain solid tumors (RECIST) version 1.0.
ORR = patients with confirmed complete or partial response.
Stable disease at 18 weeks = patients without response and with no assessment of progressive disease up to 18 weeks, but with an assessment of stable disease or better either within 2 weeks prior to the 18 week time point, or at the next non-missing assessment after the 18 week time point.
No clinical benefit = all other patients.
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18 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review
Time Frame: Week 12, Week 18
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Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause.
If a patient is not known to have died, survival was censored at the date of last contact.
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Week 12, Week 18
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Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review
Time Frame: Week 12, Week 18
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Progression-free survival (PFS) is 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 did not have an event, progression-free survival was censored at the date of last adequate tumor assessment.
A Novartis modified response evaluation criteria in solid tumors RECIST 1.1 criteria was applied to CT/MRI imaging data when assessing any responses to AUY922 treatment.
All images were evaluated locally by the investigator.
All complete or partial responses were confirmed by a second assessment at least 4 weeks later.
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Week 12, Week 18
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Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf
Time Frame: 1 hour after infusion
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Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve infinity.
There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
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1 hour after infusion
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Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast
Time Frame: 1 hour after infusion
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Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve last.
There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
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1 hour after infusion
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Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax
Time Frame: 1 hour after infusion
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Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for concentration max.
There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
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1 hour after infusion
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (ACTUAL)
August 1, 2014
Study Completion (ACTUAL)
August 1, 2014
Study Registration Dates
First Submitted
May 14, 2010
First Submitted That Met QC Criteria
May 14, 2010
First Posted (ESTIMATE)
May 17, 2010
Study Record Updates
Last Update Posted (ESTIMATE)
March 2, 2016
Last Update Submitted That Met QC Criteria
February 2, 2016
Last Verified
February 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CAUY922A2206
- 2010-020116-11 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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