Dose-escalation Study of Intravenous Liposomal Vinorelbine Tartrate Injection in Patients With Advanced Malignancy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TLC178 Liposomal Vinorelbine |
Drug: TLC178
TLC178
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) determination [4 weeks]
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.
Secondary Outcome Measures
- Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of vinorelbine[ [from day 1 to day 29]
Area under the plasma concentration time curve from zero (predose) extrapolated to infinity
- Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine [from day 1 to day 29]
Area under the plasma concentration time curve from zero (predose) extrapolated to infinity
- Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration ofvinorelbine [from day 1 to day 29]
Area under the plasma concentration time curve from zero (predose) to the time of the lastquantifiable concentration
- Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration of majormetabolite, 4-O-deacetylvinorelbine [from day 1 to day 29]
Area under the plasma concentration time curve from zero (predose) to the time of the lastquantifiable concentration
- Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of vinorelbine [from day 1 to day 29]
Maximum plasma concentration observed
- Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of vinorelbine [from day 1 to day 29]
Time of Cmax
- Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of major metabolite,4-O-deacetylvinorelbine [from day 1 to day 29]
Time of Cmax
- Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of vinorelbine [from day 1 to day 29]
Apparent terminal half life
- Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of 4-O-deacetylvinorelbine [from day 1 to day 29]
Apparent terminal half life
- Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of vinorelbine [from day 1 to day 29]
Mean residence time extrapolated to infinity
- Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of 4-O-deacetylvinorelbine [from day 1 to day 29]
Mean residence time extrapolated to infinity
- Dose exposure relationship in patients with advanced malignancies treated with single and multipledoses of LipoVNB [up to 6 months]
single and multiple dose effect
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [up to 6 months]
treatment related AE
- Incidence of Treatment-Emergent Adverse Events [up to 6 months]
TEAE percentage
- LipoVNB antitumor activity assessed by response rate [up to 6 months]
antitumor response rate
- LipoVNB antitumor activity assessed by duration of response [up to 6 months]
antitumor efficacy
- Progression free survival (PFS) of patients with advanced malignancies treated with LipoVNB [up to 6 months]
PFS
Eligibility Criteria
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
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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
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Prior radiotherapy within 4 weeks before screening
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Prior autologous stem cell transplantation within 3 months of screening and allogeneic stem cell transplantation within 6 months of screening
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More than 5 lines of previous cytotoxic therapies. For patients of CTCL who failed romidepsin, more than 4 lines of previous therapies
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Major surgery within 4 weeks prior to first administration of study drug
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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
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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
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Known HIV infection; active hepatitis B or C without concurrent treatment
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Coexistence of any active and uncontrolled infection
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Poor vital organ function defined
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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
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Known allergy or hypersensitivity to the study drug or its components
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Use of strong inhibitors or inducers of cytochrome P450 enzymes CYP3A4
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Pregnant or breast feeding women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Karmanos Cancer Center | Detroit | Michigan | United States | 48201 |
| 2 | Montefiore Medical Center | Bronx | New York | United States | 10461 |
| 3 | Taipei Veterans General Hospital | Taipei | Taiwan | 112 |
Sponsors and Collaborators
- Taiwan Liposome Company
Investigators
- Study Director: Carl Brown, Taiwan Liposome Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TLC178A1001