A Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a dose escalation study that will assess the safety and efficacy of LCL161 in combination with weekly paclitaxel in adult patients with advanced solid tumors.

Official Title
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A Phase Ib Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors

Conditions
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Solid Tumors

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 breast cancer must have a histologically or cytologically confirmed diagnosis of disease that has metastasized or is resistant to therapy. Patients with ovarian cancer must have histological evidence of recurrent epithelial ovarian, fallopian tube or peritoneal cancer. Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia Male or female patients 18 years or older ECOG performance status 0-1 Life expectancy greater than 12 weeks Measurable disease as determined by RECIST v1.0 Patients must give written informed consent and comply with the protocol Exclusion Criteria: For patients with breast cancer: Concurrent Her2-directed or anti-estrogen therapy For patients with ovarian cancer: Primary refractory disease, defined as progression during initial treatment with a platinum- and taxane-containing regimen. Prior treatment with weekly paclitaxel. More than two chemotherapy regimens given in the relapse setting. Evidence of a documented bowel obstruction within six months of study entry Patients with unresolved peripheral neuropathy, nausea, vomiting, or diarrhea ≥ CTCAE Grade 2 Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities. Patients with impairment of GI function or GI disease that may significantly alter the absorption of LCL161 Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of procedure. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β-HCG laboratory test (> 5 mIU/mL). Known diagnosis of human immunodeficiency virus (HIV) infection or chronic active hepatitis B or C (HIV and hepatitis testing are not mandatory). Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCL161 + Paclitaxel<br> | Drug: LCL161<br> <br> Drug: Paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the combination, including acute and chronic toxicities |  | 24 months | 
| Pharmacokinetics of both LCL161 and paclitaxel when administered in combination (AUC0-∞, Cmax, tmax and other parameters as appropriate) |  | 24 months | 
| Preliminary anti-tumor activity associated with this combination treatment |  | 24 months | 
| Target inhibition, cell death, and cytokines in surrogate and tumor tissues |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LCL161, solid tumors, paclitaxel