Clinical trial NCT01098838: Safety and Efficacy of LCL161 in Patients With Solid Tumors
Official title: A Phase I, Multi-center, Open-label, Dose-escalation Study of Oral LCL161 in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Cancer
adults
solid tumor
apoptosis
programmed cell death
LCL161
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-04-05
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety of increasing doses of oral LCL161 in patients with solid tumors. It is primarily designed to evaluate the side effects and find the maximum tolerated dose of LCL161.


Eligibility criteria: Inclusion Criteria:

* Solid tumor
* ECOG performance status 0-2
* Life expectancy greater than or equal to 12 weeks
* Must meet certain blood laboratory values
* Must meet criteria for time since the last dose of prior therapy
* Must provide written informed consent to participate in this study

Exclusion Criteria:

* Active and/or symptomatic brain tumors or brain metastases.
* Patients with unresolved nausea, vomiting, or diarrhea
* Any ongoing severe and/or uncontrolled medical condition that could compromise participation in the study including heart, lung or inflammatory disease
* Any disease that may significantly alter the absorption of the study drug (for example, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or removal of small bowel)
* Patients who are currently receiving treatment with steroids at a certain dose or other immunosuppressive treatment that cannot be stopped prior to starting study drug
* Patients who are currently receiving treatment with certain medications
* Patients who have received radiation therapy or have undergone major surgery within the last 4 weeks
* Women of child-bearing potential who are pregnant or breast feeding.
* Known diagnosis of human immunodeficiency virus (HIV) infection or chronic active hepatitis B or C
* Patients unwilling or unable to follow the protocol

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Occurrence of dose-limiting toxicities
timeFrame: Cycle 1
Secondary outcomes:
measure: Frequency and type of adverse events
timeFrame: throughout the study
measure: Comparison of amount of LCL161 that gets into blood stream from tablet formulation versus liquid formulation (bioavailability)
timeFrame: 3 months
measure: Blood assessments to determine how much LCL161 gets into the blood stream (pharmacokinetic parameters)
timeFrame: 4 weeks
measure: Pharmacodynamic measurements to determine how LCL161 interacts with proteins related to cancer such as cIAP, cytokines, and cell death markers; hair, skin and tumor samples will be evaluated for target inhibition
timeFrame: Intermittent throughout treatment period
measure: Solid tumor response criteria will be used to identify any anti-tumor activity
timeFrame: After a minimum of 2 cycles
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC/ Lineberger Comprehensive Cancer Center Dept. of LinbergerCancerCtr(2)
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)
state: Tennessee
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S, Cohen RB. Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2014 Oct 1;32(28):3103-10. doi: 10.1200/JCO.2013.52.3993. Epub 2014 Aug 11.