Clinical trial NCT02925000: Dose-escalation Study of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients With Advanced Malignancy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Keywords: Advanced Malignancy
lymphoma
TLC178
Lead sponsor: Taiwan Liposome Company
Sponsor class: INDUSTRY
First posted: 2016-10-05
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) determination
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of vinorelbine[
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration ofvinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of vinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of vinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of major metabolite,4-O-deacetylvinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of vinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of 4-O-deacetylvinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of vinorelbine
timeFrame: from day 1 to day 29
measure: Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of 4-O-deacetylvinorelbine
timeFrame: from day 1 to day 29
measure: Dose exposure relationship in patients with advanced malignancies treated with single and multipledoses of LipoVNB
timeFrame: up to 6 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: up to 6 months
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: up to 6 months
measure: LipoVNB antitumor activity assessed by response rate
timeFrame: up to 6 months
measure: LipoVNB antitumor activity assessed by duration of response
timeFrame: up to 6 months
measure: Progression free survival (PFS) of patients with advanced malignancies treated with LipoVNB
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taiwan Liposome Company
name: Carl Brown
role: STUDY_DIRECTOR
References: