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

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

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

Study Overview

• Status: Completed
• Conditions: Refractory Solid Tumors
• Intervention / Treatment: Drug: Nanoliposomal Irinotecan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages between 20 to 70 years old
2. Histologically or cytologically confirmed malignant solid tumors which are advanced or metastatic, have failed standard treatment or have no standard treatment currently available
3. ECOG performance status 0 or 1
4. Normal ECG or ECG without any clinically significant findings
5. 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:

1. Received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) therapy
2. Known hypersensitivity to any of the components of nal-IRI, other liposomal products, fluoropyrimidines or leucovorin
3. Have liver cirrhosis with Child-Pugh B or Child-Pugh C
4. With active CNS metastasis (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth)
5. With clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
6. Life expectancy of less than 3 months
7. Use any anti-cancer or investigational product within 14 days prior to the first date of study dosing
8. History of any second malignancy in the latest 5 years except curatively treated non-melanoma skin cancer or treated cervical carcinoma in situ
9. 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
10. 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)
11. Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanoliposomal Irinotecan + TAS-102; different dosage combination by Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)	Drug: Nanoliposomal Irinotecan; Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®); Other Names: TAS-102

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PharmaEngine
• Investigators: Principal Investigator: Chia-Chi Lin, MD, National Taiwan University Hospital, Taipei, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): October 25, 2023

Study Registration Dates

• First Submitted: December 21, 2018
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: PEP0210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No