Irinotecan Hydrochloride Liposome Injection (LY01610) For Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

PhaseⅠStudy of Irinotecan Hydrochloride Liposome Injection (LY01610) About the Safety, Tolerability, Pharmacokinetics (PK)and Preliminary Efficacy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04088604
• Other study ID #: LY01610/CT-CHN-101
• Status: Completed
• Phase: Phase 1
• Start date: February 15, 2019
• Est. completion date: December 17, 2021

Study information

• Verified date: April 2023
• Source: Luye Pharma Group Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase I, open-label, non-randomized, dose-escalation study to evaluate the safety and tolerability, the maximum tolerated dose (MTD) and the dose limited toxicity(DLT) of LY01610 monotherapy and combine with 5-Fu in patients with advanced solid tumors. Additionally, the pharmacokinetics and preliminary efficacy of LY01610 monotherapy and combine with 5-Fu will be investigated in this study.

Description:

This study will be conducted in two stages: In the first stage, ascending doses of LY01610 will be administered as monotherapy in participants with solid tumors. The starting dose was 30 mg/m2 and the subsequent dose was increased according to the protocol of 60 mg/m2, 90 mg/m2, 120 mg/m2, 150 mg/m2, 180mg/m2. Each subject received only one dose of the drug, and the next dose group study could only be performed if the previous dose group was completed 21 days of observation after the first dose and safe tolerance was confirmed. According to the subjects' tolerance, appropriate doses will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in additional 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.Another 8 subjects were enrolled and given CAMPTO® (180 mg/m2) once every 2 weeks to perform the pharmacokinetic profiles. The second stage is a dose escalation study of LY01610 combined with 5-Fu. Based on the results of the first stage, three doses of low, medium and high doses were selected in combination with a fixed dose of 5-Fu to determine the DLT and MTD. Similarly, according to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 combined with a fixed dose of 5-Fu were further evaluated in 6 - 8 patients. The drug was administered every 2 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: December 17, 2021
• Est. primary completion date: December 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female patients aged 18 to 70 years (18 years and 70 years are inclusive).
• Histologically or cytologically confirmed solid tumor for which failed or could not •tolerate standard treatment, or standard effective treatment does not exist.
• The patient should have at least one measurable lesion as the target lesion (according to RECIST 1.1 criteria).
• The predictable survival duration = 3 months.
• The Eastern Cooperative Oncology Group (ECOG) performance status score < 2 point.
• Laboratory results during screening:
• Hematology: Absolute neutrophil count = 1.5× 109/L, platelet count= 100× 109/L and hemoglobin= 90 g/L;
• Liver function: Total bilirubin(TBIL)= 1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5×ULN for the subjects without liver metastasis; ALT and AST= 5×ULN for the subjects with liver metastasis;
• Kidney function: Serum creatinine = 1.5 ×ULN or creatinine clearance rate = 50 mL/min(Cockcroft-Gault formula);
• The subject has voluntarily signed the written informed consent form (ICF) and can comply with the study protocol;
• The female subjects of childbearing age and male subjects with fertility potential female partner agree to take reliable contraceptive measures (such as abstinence, sterilizing operation, contraceptives, injection of the contraceptive drug •medroxyprogesterone acetate or subdermal implant of contraceptives) during the study period and within 6 months after infusion of the study drugs.

Exclusion Criteria:

• Patients with brain malignant tumor, lymphoma or other malignant blood diseases;
• The subjects with symptomatic brain metastasis;
• Other malignant tumors within 5 years prior to screening (except for stage Ib or lower cervical cancer, non-invasive basal cells or squamous cell skin cancer that have been cured);
• Patients with uncontrollable ascites, pleural effusion;
• Ongoing or active systemic infection need intravenous antibiotic treatment;
• Medical history of the following diseases within 6 months before screening: myocardial infarction, unstable angina, history of coronary revascularization, congestive heart failure (New York Heart Association classification = grade II), severe unstable ventricular arrhythmia, serious arrhythmia which needs drug treatment;
• The patient with hepatitis B surface antigen (HBsAg) positive and the peripheral blood HBV DNA titer =1× 103 copies/mL or 200 IU/ml The subject is eligible to be enrolled if HBsAg is positive and peripheral blood hepatitis B virus (HBV) DNA titer <1×103 copies/ml or 200 IU/ml and the investigator considers that the subject is at the stable stage of chronic hepatitis and the risk will not be increased for the subjects;the patient with hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody positive;
• Patients still with clinically significant electrolyte disorders that were diagnosed by the investigator before drug administration;

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• LY01610 ( Irinotecan hydrochloride liposome injection )
Part1-Dose Escalation and Part1-Dose Extension : subjects take LY01610;
• LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu(Fluorouracil Injection)
Part2-Dose Escalation and Part2-Dose Extension : subjects take LY01610 with 5-Fu;
• Irinotecan Hydrochloride Injection(CAMPTO®)
Irinotecan Hydrochloride Injection(CAMPTO®) pharmacokinetics comparative study

Locations

Country	Name	City	State
China	Chinese Academy of Medical Sciences and Peking Union Medical College	Peking	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Luye Pharma Group Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	The DLT of LY01610 monotherapy was obtained through the dose-increasing study of LY01610	21 days for the LY01610 monotherapy (first treatment cycle of every subjects)
Primary	Dose limiting toxicity (DLT)	The DLT of combination of LY01610 and 5-fu was obtained through the dose-increasing study of LY01610 and 5-Fu	14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects)
Primary	Maximum tolerated dose(MTD)	The MTD of LY01610 monotherapy was obtained through the single-drug dose increase study	21 days for the LY01610 monotherapy (first treatment cycle of every subjects)
Primary	Maximum tolerated dose(MTD)	The MTD of combination of LY01610 and 5-fu was obtained through the combined dose increase study	14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects)
Secondary	AUC	The AUC of LY01610 monotherapy was obtained through the dose escalation and extension study,the AUC of active comparator CAMPTO® was obtained through the study,and the AUC of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	t1/2	The t1/2 of LY01610 monotherapy was obtained through the dose escalation and extension study,the t1/2 of active comparator CAMPTO® was obtained through the study,and the t1/2 of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	Cmax	The Cmax of LY01610 monotherapy was obtained through the dose escalation and extension study,the Cmax of active comparator CAMPTO® was obtained through the study,and the Cmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	tmax	The tmax of LY01610 monotherapy was obtained through the dose escalation and extension study,the tmax of active comparator CAMPTO® was obtained through the study,and the tmax of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	Vd	The Vd of LY01610 monotherapy was obtained through the dose escalation and extension study,the Vd of active comparator CAMPTO® was obtained through the study,and the Vd of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	CL	The CL of LY01610 monotherapy was obtained through the dose escalation and extension study,the CL of active comparator CAMPTO® was obtained through the study,and the CL of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	MRT	The MRT of LY01610 monotherapy was obtained through the dose escalation and extension study,the MRT of active comparator CAMPTO® was obtained through the study,and the MRT of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	Kel	The Kel of LY01610 monotherapy was obtained through the dose escalation and extension study,the Kel of active comparator CAMPTO® was obtained through the study,and the Kel of LY01610 combined with 5-fu was obtained through the dose escalation and extension study.	22 days for the LY01610 monotherapy (first treatment cycle of every subjects),5 days for the active comparator CAMPTO® (first treatment cycle of every subjects),and 15 days for the LY01610 combined with 5-fu(first treatment cycle of every subjects)
Secondary	Best Objective Response Rate	Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu	8 weeks from enrollment
Secondary	Progression Free Survival	Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu	from the date of enrollment to the date of disease progression or death up to 24 months from randomisation of the subject
Secondary	Overall Survival	Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu	from the date of enrollment to the date of death up to 24 months from randomisation of the subject