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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02925000
• Other study ID #: TLC178A1001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 19, 2017
• Est. completion date: October 6, 2020

Study information

• Verified date: July 2021
• Source: Taiwan Liposome Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 6, 2020
• Est. primary completion date: October 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Neoplasms

Intervention

Drug:
• TLC178
TLC178

Locations

Country	Name	City	State
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Montefiore Medical Center	Bronx	New York
United States	Karmanos Cancer Center	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Taiwan Liposome Company

Countries where clinical trial is conducted

United States,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of vinorelbine	Maximum plasma concentration observed	from day 1 to day 29
Secondary	Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of vinorelbine	Time of Cmax	from day 1 to day 29
Secondary	Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of major metabolite,4-O-deacetylvinorelbine	Time of Cmax	from day 1 to day 29
Secondary	Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of vinorelbine	Apparent terminal half life	from day 1 to day 29
Secondary	Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of 4-O-deacetylvinorelbine	Apparent terminal half life	from day 1 to day 29
Secondary	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
Secondary	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
Secondary	Dose exposure relationship in patients with advanced malignancies treated with single and multipledoses of LipoVNB	single and multiple dose effect	up to 6 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	treatment related AE	up to 6 months
Secondary	Incidence of Treatment-Emergent Adverse Events	TEAE percentage	up to 6 months
Secondary	LipoVNB antitumor activity assessed by response rate	antitumor response rate	up to 6 months
Secondary	LipoVNB antitumor activity assessed by duration of response	antitumor efficacy	up to 6 months
Secondary	Progression free survival (PFS) of patients with advanced malignancies treated with LipoVNB	PFS	up to 6 months