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

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ClinicalTrials.gov Identifier: NCT02925000
Recruitment Status : Recruiting
First Posted : October 5, 2016
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Taiwan Liposome Company

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
Cancer Drug: TLC178 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 19, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TLC178
Liposomal Vinorelbine
Drug: TLC178
TLC178
Other Name: Liposomal Vinorelbine




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) determination [ Time Frame: 4 weeks ]
    To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of intravenous LipoVNB given every 4 weeks (Q4W) in patients with advanced malignancies.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Area under the plasma concentration time curve from zero (predose) extrapolated to infinity

  2. Pharmacokinetics (PK) parameters of AUC (0-inf) calculated by plasma concentration of major metabolite, 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Area under the plasma concentration time curve from zero (predose) extrapolated to infinity

  3. Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Area under the plasma concentration time curve from zero (predose) to the time of the last quantifiable concentration

  4. Pharmacokinetics (PK) parameters of AUC(0 - last) calculated by plasma concentration of major metabolite, 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Area under the plasma concentration time curve from zero (predose) to the time of the last quantifiable concentration

  5. Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Maximum plasma concentration observed

  6. Pharmacokinetics (PK) parameters of Cmax calculated by plasma concentration of major metabolite, 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Maximum plasma concentration observed

  7. Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Time of Cmax

  8. Pharmacokinetics (PK) parameters of tmax calculated by plasma concentration of major metabolite, 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Time of Cmax

  9. Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Apparent terminal half life

  10. Pharmacokinetics (PK) parameters of t1/2 calculated by plasma concentration of 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Apparent terminal half life

  11. Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of vinorelbine [ Time Frame: from day 1 to day 29 ]
    Mean residence time extrapolated to infinity

  12. Pharmacokinetics (PK) parameters of MRT(0-inf) calculated by plasma concentration of 4-O-deacetylvinorelbine [ Time Frame: from day 1 to day 29 ]
    Mean residence time extrapolated to infinity

  13. Dose exposure relationship in patients with advanced malignancies treated with single and multiple doses of LipoVNB [ Time Frame: from day 1 to day 29 ]
    single and multiple dose effect

  14. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: up to 6 months ]
    treatment related AE

  15. Incidence of Treatment-Emergent Adverse Events [ Time Frame: up to 6 months ]
    TEAE percentage

  16. LipoVNB antitumor activity assessed by response rate [ Time Frame: up to 6 months ]
    antitumor response rate

  17. LipoVNB antitumor activity assessed by duration of response [ Time Frame: up to 6 months ]
    antitumor efficacy

  18. Progression free survival (PFS) of patients with advanced malignancies treated with LipoVNB [ Time Frame: up to 6 months ]
    PFS



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Male or female, ≥18 years of age (≥20 years of age in Taiwan)
  2. Patients with histologically/cytologically confirmed solid tumor, or lymphoma. For the expansion cohort, only patients with peripheral/cutaneous T cell lymphoma, Hodgkin's lymphoma, and other non-Hodgkin's lymphoma would be considered eligible
  3. 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
  4. Assessable disease status defined by Cheson (for lymphoma) or modified severity weighted assessment tool (mSWAT) (for mycosis fungoides [MF] and Sezary syndrome [SS]) criteria, or having measurable tumors defined by Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1) (for solid tumor)
  5. Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2
  6. Anticipated life expectancy of more than 3 months per Investigator's judgement
  7. Women of childbearing potential must have a negative urine pregnancy test at the screening visit
  8. Male patients with female partners of childbearing potential, and female patients of childbearing potential must agree to use effective birth control. Effective birth control and cessation of lactation must be complied at least 2 weeks prior to first study drug administration, during the trial participation, and for 3 months after the last dose of study drug
  9. Willing and able to comply with the study procedure and sign a written informed consent

Exclusion Criteria:

  1. Patient with untreated or inadequate controlled brain metastases. Brain metastases or lymphoma with CNS involvement previously treated by radiotherapy or other modality and stable for at least 3 months prior to screening without requirement of corticosteroids or anticonvulsants are permitted
  2. 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
  3. More than 5 lines of previous cytotoxic therapies. For patients of CTCL who failed romidepsin, more than 4 lines of previous therapies
  4. Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 2 years before screening. Limited field radiation for ≤2 weeks prior to screening period is permitted
  5. Any toxicity due to prior therapy that has not been resolved to less than Grade 2 severity by Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03 or higher) criteria
  6. Medical history of uncontrolled but clinically significant abnormal cardiac conduction abnormalities at electrocardiogram (ECG), 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
  7. Poor vital organ function defined as:

    • Absolute neutrophil count (ANC) <1,500/mm3, pre-transfusion platelets <100,000/mm3, or pre-transfusion hemoglobin <9.0 mg/dL (the patient is required to have at least 2 weeks free from blood transfusion, G-CSF and erythropoietin use prior to the hematology test)
    • International Normalized Ratio (INR) for coagulation above upper normal range
    • Total bilirubin >1.5 times upper limit of normal (ULN)
    • Aspartate amino transferase (AST) or Alanine amino transferase (ALT) >3 times ULN in patient without liver metastasis or liver cirrhosis
    • Child Pugh B or C stage liver disease
    • Creatinine clearance (by Cockcroft Gault formula) <40 mL/min
  8. Use of potent inhibitors or inducers of cytochrome P450 enzymes CYP3A4 within 14 days prior to first study 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): NCT02925000


Contacts
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Contact: Renee Chih 886 2 26557377 renee@tlcbio.com
Contact: Karen Chen karen_chen@tlcbio.com

Locations
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United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Ulka Vaishampayan         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Contact: Sanjay Goel         
Taiwan
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 10048
Contact: Chia-Chi Lin         
Sponsors and Collaborators
Taiwan Liposome Company
Investigators
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Study Director: Karen Chen Taiwan Liposome Company

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Responsible Party: Taiwan Liposome Company
ClinicalTrials.gov Identifier: NCT02925000     History of Changes
Other Study ID Numbers: TLC178A1001
First Posted: October 5, 2016    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Taiwan Liposome Company:
Advanced Malignancy
lymphoma
TLC178

Additional relevant MeSH terms:
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Neoplasms
Vinorelbine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action