Irinotecan Hydrochloride Liposome Injection (LY01610) For Advanced Solid Tumors

NCT04088604 | Completed Phase 1

• 1 other identifier: LY01610/CT-CHN-101
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

LY01610; 5-Fu; Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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 Outcomes (11)

• AUC

  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)

• t1/2

  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)

• Cmax

  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)

• tmax

  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)

• Vd

  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)

Study Arms (5)

LY01610-Dose Escalation

EXPERIMENTAL

The starting dose was 30 mg/m2 IV 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. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.

Drug: LY01610 ( Irinotecan hydrochloride liposome injection )

LY01610-Dose Extension

EXPERIMENTAL

According to the subjects' tolerance, appropriate dose will be selected and the safety, PK characteristics and initial efficacy of LY01610 were further evaluated in 6 - 8 patients. The interval between the first dose and the second dose was 3 weeks, followed by 2 weeks.

Drug: LY01610 ( Irinotecan hydrochloride liposome injection )

LY01610 with 5-Fu -Dose Escalation

EXPERIMENTAL

Dose Escalation: 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, MTD, PK characteristics and the preliminary efficacy. 5-Fu, 400mg/m2 will be administered intravenously on days 1, followed by 600 mg/m2 given as a 22-hour continuous infusion on day 1 and 2, every 2 weeks.

Drug: LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu（Fluorouracil Injection）

LY01610 with 5-Fu -Dose Extension

EXPERIMENTAL

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 additional 6 - 8 patients. In dose escalation and dose extension stages, both LY01610 and fixed dose 5-Fu will be given once every 2 weeks.

Drug: LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu（Fluorouracil Injection）

Hydrochloride Injection- pharmacokinetics comparative study

ACTIVE COMPARATOR

After receiving the MTD of LY01610, another 8 subjects were enrolled and given Irinotecan Hydrochloride Injection（captol ®） (180mg/m2) once every 2 weeks. Upon completion of the pharmacokinetics study, the sponsor will continue to provide the study drug treatment free of charge, and the researcher will conduct treatment and examination according to the subject's situation, without collecting any safety and efficacy data of the subject.

Drug: Irinotecan Hydrochloride Injection（CAMPTO®）

Interventions

LY01610 ( Irinotecan hydrochloride liposome injection ) DRUG

Part1-Dose Escalation and Part1-Dose Extension : subjects take LY01610;

LY01610-Dose Escalation; LY01610-Dose Extension

LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu（Fluorouracil Injection） DRUG

Part2-Dose Escalation and Part2-Dose Extension : subjects take LY01610 with 5-Fu;

LY01610 with 5-Fu -Dose Escalation; LY01610 with 5-Fu -Dose Extension

Irinotecan Hydrochloride Injection（CAMPTO®） DRUG

Irinotecan Hydrochloride Injection（CAMPTO®） pharmacokinetics comparative study

Hydrochloride Injection- pharmacokinetics comparative study

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead

Study Sites (1)

Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

Location

Related Publications (1)

• Liu Y, Zhang B, Xu J, Wang X, Tang J, Huang J. Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma. Cancer Chemother Pharmacol. 2021 Sep;88(3):403-414. doi: 10.1007/s00280-021-04294-2. Epub 2021 May 24.

  PMID: 34031756 DERIVED

Study Officials

• Huang jing

  Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None，Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: September 13, 2019
• Study Start: February 15, 2019
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)