Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors

Study Overview
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Brief Summary
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The study is to explore the combination of nal-IRI and TAS-102, which is expected to be an effective regimen that could be applied to various cancers

Detailed Description
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Primary Objectives to determine the maximum tolerated dose (MTD) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) to evaluate the toxicity profile of the combination therapy Secondary Objectives to evaluate the preliminary efficacy of the combination therapy of nal-IRI (ONIVYDE®) and TAS-102 (LONSURF®) to study the pharmacokinetics of the combination therapy A phase 1 study with a classical 3 + 3 dose escalation design. The target population is patients who have pathologically confirmed malignant solid tumors with no standard treatment available.

Official Title
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Phase 1 Study of Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors

Conditions
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Refractory Solid Tumors

Intervention / Treatment
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* Drug: Nanoliposomal Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages between 20 to 70 years old Histologically or cytologically confirmed malignant solid tumors which are advanced or metastatic, have failed standard treatment or have no standard treatment currently available ECOG performance status 0 or 1 Normal ECG or ECG without any clinically significant findings Adequate hematologic parameters, and hepatic and renal function i. White blood cell (WBC) count 3000/μL and absolute neutrophil count (ANC) 1500/μL ii. Platelet counts 100,000/μL without platelet transfusion within 14 days iii. Hemoglobin level 10 g/dL iv. Serum total bilirubin- within normal range v. Serum albumin 3.0 g/dL vi. Serum alanine aminotransferase (ALT) 3 x the upper limit of normal (ULN) vii. Serum creatinine 1.5 x ULN Exclusion Criteria: Received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) therapy Known hypersensitivity to any of the components of nal-IRI, other liposomal products, fluoropyrimidines or leucovorin Have liver cirrhosis with Child-Pugh B or Child-Pugh C With active CNS metastasis (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth) With clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1 Life expectancy of less than 3 months Use any anti-cancer or investigational product within 14 days prior to the first date of study dosing History of any second malignancy in the latest 5 years except curatively treated non-melanoma skin cancer or treated cervical carcinoma in situ Uncontrolled inter-current illness including, but not limited to, ongoing or active infection requiring antibiotic treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia, and psychiatric illness or social situation that would preclude study compliance Homozygous for the UGT1A1 28 allele (TA7/TA7), homozygous for UGT1A1 6 allele (A/A), or double heterozygous for both UGT1A1 28 allele (TA6/TA7) and UGT1A1 6 allele (G/A) (only for dose-finding phase) Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Nanoliposomal Irinotecan + TAS-102<br>different dosage combination by Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®) | Drug: Nanoliposomal Irinotecan<br>* Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)<br>* Other names: TAS-102;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Dose Limiting Toxicities (DLT) | to find the Dose Limiting Toxicity (DLT) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) | 12 months | 
| Evaluation of Safety profile of nal-IRI and TAS-102 - Incidence of Treatment-Emergent Adverse Events | Incidence of Treatment-Emergent Adverse Events [Safety] of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) according to NCI-CTCAE version 5.0 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST) | the objective tumor rate by using RECIST v1.1 | 24 months | 
| Pharmacokinetics study - (Cmax) | Concentration of Peak Plasma (Cmax) | 6 months | 
| Pharmacokinetics study - (Tmax) | maximum concentration of the time taken to reach the (Tmax). | 6 months | 
| Pharmacokinetics study - (T1/2) | time of C max to drop in half taken (T1/2) | 6 months | 
| Pharmacokinetics study - (AUC0→t) | area of the plasma concentration versus time curve (AUC0→t). | 6 months | 
| Pharmacokinetics study - (AUC0→∞) | area of the plasma concentration versus under curve (AUC0→∞) | 6 months | 
| Pharmacokinetics study - (CL) | rate of clearance (CL) | 6 months |