Safety and Tolerability of Oral LCL161 in Japanese Adult Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate safety and tolerability to estimate the maximum tolerated dose and/or recommended dose of oral LCL161 in Japanese patients with advanced solid tumors.

Official Title
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A Phase I Study of Oral LCL161 in Japanese Adult Patients With Advanced Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: LCL161
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with a histologically or cytologically confirmed diagnosis of a solid tumor for which no further effective standard treatment is available. ECOG performance status 0-1. Patients must have recovered from all toxicities related to their previous treatment. Exclusion criteria: Unresolved nausea, vomiting, diarrhea or peripheral neuropathy CTCAE grade >1. History of or current interstitial lung disease or autoimmune disease. History of or current impaired cardiac function or clinically significant cardiac diseases. Women of child-bearing potential, unless they are using highly effective methods of contraception. 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: LCL161<br>Dose escalation part: Eligible patients will start to receive oral LCL161 once a week and will receive weekly paclitaxel, at 80 mg/m2 intravenous infusion over 1 hour, in combination with LCL161 from cycle 2. Dose expansion part: Eligible patients will receive oral LCL161 at the maximum tolerated dose and/or recommended dose in combination with weekly paclitaxel, at 80 mg/m2 intravenous infusion over 1 hour from cycle 1. | Drug: LCL161<br>* Patients will receive oral LCL161 once a week until unacceptable toxicity, disease progression and/or withdrawal of consent.<br>Drug: Paclitaxel<br>* Patients will receive weekly paclitaxel as intravenous infusion over 1 hour in combination with LCL161, from cycle 2 in dose escalation part or from the first cycle in dose expansion part, and will continue it until unacceptable toxicity, disease progression and/or withdrawal of consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of dose limiting toxicities as a function of LCL161 during first cycle |  | First cycle (21 days) | 
| Adverse events of oral LCL161 | Type and frequency of adverse events of oral LCL161 when administered in combination with weekly paclitaxel | From informed consent until 28 days after end of treatment (end of treatment visit occurs within 7 days after the determination of study discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of oral LCL161 | Type and frequency of adverse events of oral LCL161 | From informed consent until 28 days after end of treatment (end of treatment visit occurs within 7 days after the determination of study discontinuation) | 
| LCL161 plasma concentration and derived pharmacokinetic parameters |  | From first cycle and up to 3 cycle (each cycle is 21-day period) | 
| Paclitaxel plasma concentration and derived pharmacokinetic parameters |  | From first cycle of combination and up to 2 cycle (each cycle is 21-day period) | 
| Tumor response according to RECIST 1.1 |  | Every 2 cycles for first 8 cycles, then every 3 cycles and until end of treatment (each cycle is 21-day period and end of treatment visit occurs within 7 days after the determination of study discontinuation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LCL161, Paclitaxel, Japanese patient, Neoplasms