A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy.

Non-small-cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124864
• Other study ID #: CAUY922A2206
• Secondary ID: 2010-020116-11
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2010
• Last updated: February 2, 2016
• Start date: October 2010
• Est. completion date: August 2014

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNetherlands: Medicines Evaluation Board (MEB)Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)Canada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesNorway: Norwegian Medicines AgencySouth Korea: Korea Food and Drug Administration (KFDA)Spain: Ministry of HealthTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small-cell Lung Cancer

Intervention

Drug:
• AUY922
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.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Montreal	Quebec
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Marseille cedex 20
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Oldenburg
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Groningen
Norway	Novartis Investigative Site	Oslo
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Turkey	Novartis Investigative Site	Izmir
United States	St. Luke's Hospital and Health Network St Luke's	Bethlehem	Pennsylvania
United States	Dana Farber Cancer Institute DFCI	Boston	Massachusetts
United States	University of California at Los Angeles UCLA - Santa Monica	Los Angeles	California
United States	Maryland Oncology Hematology, P.A. Dept. of Assoc. Onc/Hem	Rockville	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Korea, Republic of,  Netherlands,  Norway,  Singapore,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Assessment by Study Stratum - Per Investigator Assessment	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.	18 weeks	No
Secondary	Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review	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.	Week 12, Week 18	No
Secondary	Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review	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.	Week 12, Week 18	No
Secondary	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf	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.	1 hour after infusion	No
Secondary	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast	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.	1 hour after infusion	No
Secondary	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax	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.	1 hour after infusion	No