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Irinotecan Hydrochloride Liposome Injection (LY01610) For Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04088604
Recruitment Status : Recruiting
First Posted : September 13, 2019
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Luye Pharma Group Ltd.

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: LY01610 ( Irinotecan hydrochloride liposome injection ) Drug: LY01610 ( Irinotecan hydrochloride liposome injection ) with 5-Fu(Fluorouracil Injection) Drug: Irinotecan Hydrochloride Injection(CAMPTO®) Phase 1

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 111 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel
Masking: None (Open Label)
Masking Description: None,Open Label
Primary Purpose: Treatment
Official Title: PhaseⅠStudy of Irinotecan Hydrochloride Liposome Injection (LY01610) About the Safety, Tolerability, Pharmacokinetics (PK)and Preliminary Efficacy in Patients With Advanced Solid Tumors
Actual Study Start Date : February 15, 2019
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : February 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LY01610-Dose Escalation
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 )
Part1-Dose Escalation and Part1-Dose Extension : subjects take LY01610;

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

Experimental: LY01610 with 5-Fu -Dose Escalation

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

Experimental: LY01610 with 5-Fu -Dose Extension

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

Active Comparator: Hydrochloride Injection- pharmacokinetics comparative study
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®)
Irinotecan Hydrochloride Injection(CAMPTO®) pharmacokinetics comparative study




Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) [ Time Frame: 21 days for the LY01610 monotherapy (first treatment cycle of every subjects) ]
    The DLT of LY01610 monotherapy was obtained through the dose-increasing study of LY01610

  2. Dose limiting toxicity (DLT) [ Time Frame: 14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects) ]
    The DLT of combination of LY01610 and 5-fu was obtained through the dose-increasing study of LY01610 and 5-Fu

  3. Maximum tolerated dose(MTD) [ Time Frame: 21 days for the LY01610 monotherapy (first treatment cycle of every subjects) ]
    The MTD of LY01610 monotherapy was obtained through the single-drug dose increase study

  4. Maximum tolerated dose(MTD) [ Time Frame: 14 days for the LY01610 combined 5-Fu (first treatment cycle of every subjects) ]
    The MTD of combination of LY01610 and 5-fu was obtained through the combined dose increase study


Secondary Outcome Measures :
  1. AUC [ Time Frame: 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) ]
    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.

  2. t1/2 [ Time Frame: 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) ]
    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.

  3. Cmax [ Time Frame: 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) ]
    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.

  4. tmax [ Time Frame: 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) ]
    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.

  5. Vd [ Time Frame: 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) ]
    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.

  6. CL [ Time Frame: 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) ]
    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.

  7. MRT [ Time Frame: 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) ]
    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.

  8. Kel [ Time Frame: 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) ]
    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.

  9. Best Objective Response Rate [ Time Frame: 8 weeks from enrollment ]
    Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu

  10. Progression Free Survival [ Time Frame: from the date of enrollment to the date of disease progression or death up to 24 months from randomisation of the subject ]
    Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu

  11. Overall Survival [ Time Frame: from the date of enrollment to the date of death up to 24 months from randomisation of the subject ]
    Preliminary efficacy evaluation of LY01610 and LY01610 combined with 5-fu



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04088604


Contacts
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Contact: Jiang jiling +86-13311538756 jiangjiling@luye.com
Contact: Liu enyi +86-18701645393 liuenyi@luye.com

Locations
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China, Beijing
Chinese Academy of Medical Sciences and Peking Union Medical College Recruiting
Peking, Beijing, China, 100021
Contact: Li ning    +86 010-87788888    Lining@cicams.ac.cn   
Sponsors and Collaborators
Luye Pharma Group Ltd.
Investigators
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Principal Investigator: Huang jing Chinese Academy of Medical Sciences and Peking Union Medical College

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Responsible Party: Luye Pharma Group Ltd.
ClinicalTrials.gov Identifier: NCT04088604     History of Changes
Other Study ID Numbers: LY01610/CT-CHN-101
First Posted: September 13, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Luye Pharma Group Ltd.:
LY01610
5-Fu
Safety
Tolerability
Pharmacokinetics
Additional relevant MeSH terms:
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Neoplasms
Irinotecan
Fluorouracil
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs