Clinical trial NCT01772797: Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer
Official title: A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anaplastic Lymphoma Kinase (ALK)
Non-small Cell Lung Cancer
Keywords: anaplastic lymphoma kinase, ALK-rearranged lung cancer, non-small cell lung cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-01-21
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence rate of Dose Limiting Toxicities (DLT)
timeFrame: up to day 28 after the patient's first dose
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: 30 months
measure: Changes in laboratory values
timeFrame: 30 months
measure: Assessments of electrocardiograms
timeFrame: 30 months
measure: Assessments of dose interruptions, reductions, and dose intensity
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: Tmax
timeFrame: 30 months
measure: Overall response rate (ORR)
timeFrame: 30 months
measure: Duration of Response (DoR)
timeFrame: 30 months
measure: Time to Response (TTR)
timeFrame: 30 months
measure: Progression free survival (PFS)
timeFrame: 30 months
measure: Number of patients with serious adverse events
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: Cmax
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: AUClast
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: AUCtau
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: Cmin
timeFrame: 30 months
measure: Plasma PK parameter of LDK378 and AUY922: Racc
timeFrame: 30 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Dept. of Anschutz Cancer (3)
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General
state: Massachusetts
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center Fox Chase Cancer (2)
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman
state: Utah
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: