Safety and Efficacy of LCL161 in Patients With Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Multi-center, Open-label, Dose-escalation Study of Oral LCL161 in Adult Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: LCL161


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weekly dosing of LCL161<br>by mouth (oral) | Drug: LCL161<br> <br> |
| Experimental: Comparison of LCL161<br>tablet versus liquid | Drug: LCL161<br> <br> |
| Experimental: Twice daily dosing of LCL161<br>by mouth for 4 days followed by a 3-day rest period every week | Drug: LCL161<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of dose-limiting toxicities |  | Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and type of adverse events |  | throughout the study | 
| Comparison of amount of LCL161 that gets into blood stream from tablet formulation versus liquid formulation (bioavailability) |  | 3 months | 
| Blood assessments to determine how much LCL161 gets into the blood stream (pharmacokinetic parameters) |  | 4 weeks | 
| 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 |  | Intermittent throughout treatment period | 
| Solid tumor response criteria will be used to identify any anti-tumor activity |  | After a minimum of 2 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apoptosis, Cancer, adults, solid tumor, programmed cell death, LCL161