Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01772797
• Other study ID #: CLDK378X2102
• Secondary ID: 2012-004632-29
• Status: Completed
• Phase: Phase 1
• Start date: June 2013
• Est. completion date: January 2016

Study information

• Verified date: September 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• locally advanced or metastatic NSCLC that has progressed during or following therapy with an ALK inhibitor

• tumor must carry an ALK rearrangement in 15% or more of tumor cells as measured by FISH

• disease that can be evaluated by RECIST v1.1 and measurable disease

Exclusion Criteria:

• central nervous system (CNS) metastases that are symptomatic or require increasing steroids or CNS-directed therapy to control CNS disease

• history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis

• clinically significant cardiac dysfunction

• inadequate end organ function as defined by specified laboratory values

• use of medications known to be strong inhibitors or inducters of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment

• use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment

• clinically significant, uncontrolled impaired gastrointestinal function or GI disease

• prior treatment with a HSP90 inhibitor

• radiotherapy to lung within 4 weeks prior to the first dose of study treatment or patients who have not recovered from radiotherapy-related toxicities

• pregnant or nursing women

• history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.

Related Conditions & MeSH terms

• Anaplastic Lymphoma Kinase (ALK)
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• LDK378
LDK378 is a capsule to be taken daily by mouth.
• AUY922
AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Italy	Novartis Investigative Site	Milano	MI
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
United States	University of Colorado Dept. of Anschutz Cancer (3)	Aurora	Colorado
United States	Massachusetts General Hospital Mass General	Boston	Massachusetts
United States	Fox Chase Cancer Center Fox Chase Cancer (2)	Philadelphia	Pennsylvania
United States	University of Utah / Huntsman Cancer Institute Huntsman	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of Dose Limiting Toxicities (DLT)	cycle = within the first 28 days of patient's first dose	up to day 28 after the patient's first dose
Secondary	Number of patients with adverse events	Characterize the safety and tolerability of LDK378 and AUY922 in patients	30 months
Secondary	Changes in laboratory values	Characterize the safety and tolerability of LDK378 and AUY922 in patients	30 months
Secondary	Assessments of electrocardiograms	Characterize the safety and tolerability of LDK378 and AUY922 in patients	30 months
Secondary	Assessments of dose interruptions, reductions, and dose intensity	Characterize the safety and tolerability of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: Tmax	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months
Secondary	Overall response rate (ORR)	Assess the anti-tumor activity of LDK378 and AUY922	30 months
Secondary	Duration of Response (DoR)	Assess the anti-tumor activity of LDK378 and AUY922	30 months
Secondary	Time to Response (TTR)	Assess the anti-tumor activity of LDK378 and AUY922	30 months
Secondary	Progression free survival (PFS)	Assess the anti-tumor activity of LDK378 and AUY922 per RECIST 1.1	30 months
Secondary	Number of patients with serious adverse events	Characterize the safety and tolerability of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: Cmax	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: AUClast	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: AUCtau	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: Cmin	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months
Secondary	Plasma PK parameter of LDK378 and AUY922: Racc	Characterize single and multiple dose PK of LDK378 and AUY922 in patients	30 months

External Links

•   Results for CLDK378X2102 can be found on the Novartis Clinical Trial Results Website