A Study of Irinotecan Hydrochloride Liposome in Combination With 5-FU/LV in Advanced Solid Tumors

A Phase Ib Study to Evaluate Tolerability, Safety and Pharmacokinetics of Irinotecan Hydrochloride Liposome Injection in Combination With 5-FU/LV in Patients With Advanced Solid Tumors

This is a dose-escalation and expansion, open label, single centre, phase Ib study. In this study, the tolerability, safety, pharmacokinetics and efficacy of irinotecan hydrochloride liposome injection in combination with 5-FU/LV were studied in patients with advanced solid tumors. Meanwhile, to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of irinotecan hydrochloride liposome.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Irinotecan liposome、5-fluorouracil、Leucovorin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumors documented as advanced or metastatic disease;
2. Subjects must be considered relapsed or refractory to standard therapies, have been intolerant to standard therapies, or have refused standard therapy;
3. ECOG: 0-1;
4. Adequate organ and bone marrow function;
5. sign an informed consent.

Exclusion Criteria:

1. Patients with brain malignant tumor or active CNS metastasis;
2. UGT1A1*28 homozygous mutants;
3. Clinically significant GI disorders;
4. Significant cardiovascular disease;
5. Active infection or uncontrolled fever;
6. Pregnant or breast feeding patients;
7. Allergic to a drug ingredient or component;
8. The investigators determined that other conditions were inappropriate for participation in this clinical trial.

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: Treatment group: Irinotecan liposome plus 5-fluorouracil, Leucovorin	Drug: Irinotecan liposome、5-fluorouracil、Leucovorin; Irinotecan liposome、5-fluorouracil、Leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event (AE)	Assessed by CTCAE v4.03	Assessed from study inclusion to 30 days after last dose
Dose Limiting Toxicities (DLT)	Dose Limiting Toxicities for patients in combination treatment	DLTs will be evaluated during 28-day period following the first dose of study treatment
Maximal tolerated dose (MTD)	Maximum tolerated dose for patients in combination treatment	after the last patient in each cohort up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurs first.	The maximum time in follow up was 12 months
Objective Response Rate	Objective response rate was based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	maximum time on study 12 months
Time to reach maximum plasma concentration (Tmax)	Tmax of total irinotecan, free irinotecan and SN-38	up to 168 hours after the first dose
Maximum observed plasma concentration (Cmax)	Cmax of total irinotecan, free irinotecan and SN-38	up to 168 hours after the first dose
Area under the plasma concentration versus time curve from time zero to time of last observed concentration (AUC0-t)	AUC0-t of total irinotecan, free irinotecan and SN-38	up to 168 hours after the first dose
Area under the plasma concentration versus time curve from time zero to infinity (AUC0-inf)	AUC0-inf of total irinotecan, free irinotecan and SN-38	up to 168 hours after the first dose
Elimination half-life (T1/2)	T1/2 of total irinotecan, free irinotecan and SN-38	up to 168 hours after the first dose
Clearance of drug from plasma (CL)	CL of total irinotecan	up to 168 hours after the first dose
Volume of distribution (Vss)	Vss of total irinotecan	up to 168 hours after the first dose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2016
• Primary Completion (Actual): June 6, 2018
• Study Completion (Actual): June 6, 2018

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 21, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan
• Other Study ID Numbers: YLTKL-Ib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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