Dose-escalation Study of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients With Advanced Malignancy

A Phase I/IIa, Open Label, Dose-escalation Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients With Advanced Malignancy

This is a phase I/IIa, Open label, Dose-escalation Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients with Advanced Malignancy.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: TLC178

Detailed Description

Protocol No: TLC178A1001

Name of Finished Product: LipoVNB (Liposomal Vinorelbine Tartrate)

Title of Study:

Phase I/IIa, Open label, Dose-escalation Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients with Advanced Malignancy.

Study duration:

Every patient will have a treatment period of 4-week cycles until completion of 6 cycles, progression of disease or intolerance, withdrawal of consent or Investigator's judgment, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center

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

• Male or female, ≥18 years of age (≥20 years of age in Taiwan)
• Patients with histologically/cytologically confirmed solid tumor, or lymphoma including PTCL or CTCL.
• Malignancies for which there is no standard therapy, or previously treated locally advanced, refractory/relapsed or metastatic disease for which local curative surgery, curable radiotherapy, or satisfactory systemic anticancer therapy is no longer available
• Having at least one measurable tumor
• ECOG Performance Status of ≤2
• Women of childbearing potential must have a negative pregnancy test.

Exclusion Criteria

• Patient with untreated or inadequate controlled brain metastases.
• Prior systemic standard or investigational anticancer therapy, including target therapy, chemotherapy, immunotherapy within 28 days prior to the first dose of study drug. The above mentioned conditions which the Investigator considers there is no more drug effect, such as ≥5 half-lives are permitted
• Prior radiotherapy within 4 weeks before screening
• Prior autologous stem cell transplantation within 3 months of screening and allogeneic stem cell transplantation within 6 months of screening
• More than 5 lines of previous cytotoxic therapies. For patients of CTCL who failed romidepsin, more than 4 lines of previous therapies
• Major surgery within 4 weeks prior to first administration of study drug
• History of myocardial infarction, unstable angina or severe congestive heart failure (New York Heart Classification Class IV) or major stroke within 3 months prior to screening period
• Medical history of uncontrolled but clinically significant abnormal cardiac conduction abnormalities at electrocardiogram (ECG) at screening, any history or evidence of long QT syndrome or QTcF interval >450 msec for males and >470 msec for females (according to Fridericia's correction) at screening
• Known HIV infection; active hepatitis B or C without concurrent treatment
• Coexistence of any active and uncontrolled infection
• Poor vital organ function defined
• Uncontrolled and unstable concurrent medical condition including psychiatric disorders and alcohol/substance dependence/abuse that will jeopardize the safety of the patient, interfere with the objectives of the study, or affect the patient compliance with study requirements, as determined by the Investigator
• Known allergy or hypersensitivity to the study drug or its components
• Use of strong inhibitors or inducers of cytochrome P450 enzymes CYP3A4
• Pregnant or breast feeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TLC178; Liposomal Vinorelbine	Drug: TLC178; TLC178; Other Names: Liposomal Vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) determination	To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) ofintravenous LipoVNB given every 4 weeks (Q4W) in patients with advanced malignancies.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of vinorelbine[	Area under the plasma concentration time curve from zero (predose) extrapolated to infinity	from day 1 to day 29
Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine	Area under the plasma concentration time curve from zero (predose) extrapolated to infinity	from day 1 to day 29
Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration ofvinorelbine	Area under the plasma concentration time curve from zero (predose) to the time of the lastquantifiable concentration	from day 1 to day 29
Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine	Area under the plasma concentration time curve from zero (predose) to the time of the lastquantifiable concentration	from day 1 to day 29
Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of vinorelbine	Maximum plasma concentration observed	from day 1 to day 29
Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of vinorelbine	Time of Cmax	from day 1 to day 29
Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of major metabolite,4-O-deacetylvinorelbine	Time of Cmax	from day 1 to day 29
Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of vinorelbine	Apparent terminal half life	from day 1 to day 29
Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of 4-O-deacetylvinorelbine	Apparent terminal half life	from day 1 to day 29
Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of vinorelbine	Mean residence time extrapolated to infinity	from day 1 to day 29
Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of 4-O-deacetylvinorelbine	Mean residence time extrapolated to infinity	from day 1 to day 29
Dose exposure relationship in patients with advanced malignancies treated with single and multipledoses of LipoVNB	single and multiple dose effect	up to 6 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	treatment related AE	up to 6 months
Incidence of Treatment-Emergent Adverse Events	TEAE percentage	up to 6 months
LipoVNB antitumor activity assessed by response rate	antitumor response rate	up to 6 months
LipoVNB antitumor activity assessed by duration of response	antitumor efficacy	up to 6 months
Progression free survival (PFS) of patients with advanced malignancies treated with LipoVNB	PFS	up to 6 months

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Carl Brown, Taiwan Liposome Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 19, 2017
• Primary Completion (ACTUAL): October 6, 2020
• Study Completion (ACTUAL): October 6, 2020

Study Registration Dates

• First Submitted: August 23, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (ESTIMATE): October 5, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: lymphoma; Advanced Malignancy; TLC178
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: TLC178A1001

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