Assess Bioequivalence of Two Formulations of Doxorubicin Hydrochloride Liposome in Female Patients With Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a multi-center, single-dose, open-label, randomized, balanced, two-treatment,
      two-cycle, two-sequence crossover study to assess bioequivalence of test (T) and reference
      (R) formulations of doxorubicin hydrochloride liposome injection in female patients with
      ovarian cancer.

      Each patient will be randomized to one of two treatment sequences (RT or TR) according to a
      randomization scheme prepared prior to the start of the trial.There will be at least 4-week
      apart between each single-dose administration. Serial blood samples for determination of free
      doxorubicin and liposomal encapsulated doxorubicin plasma concentrations for PK analysis will
      be obtained in each cycle.

      The 90% confidence intervals on the GMR(geometric mean ratio) of test to reference products
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate
      bioequivalence.
    

Detailed description: 
      This study has an adaptive 2-stage design. Bioequivalence based on encapsulated doxorubicin
      will be tested at the end of Stage 1 . An interim analysis of free doxorubicin will be
      performed at the end of Stage 1 . If needed, the study may continue into Stage 2 with
      additional number of ovarian cancer patients determined based on the interim analysis; and a
      final evaluation of bioequivalence for free doxorubicin will be performed at the end of Stage
      2. Each patient will be randomized to one of two treatment sequences (RT or TR) according to
      a randomization scheme prepared prior to the start of the trial. Serial blood samples for
      determination of free doxorubicin and liposomal encapsulated doxorubicin plasma
      concentrations for PK analysis will be obtained in each cycle.

      The 90% confidence intervals on the GMR（geometric mean ratio） of test to reference products
      of free and liposome encapsulated doxorubicin for PK must be within 80-125% to demonstrate
      bioequivalence.

      Safety data will be summarized and listed. Adverse events will be coded and classified by
      system organ class and preferred term using Common Terminology Criteria for Adverse Events. A
      summary of all drug-related adverse events will also be generated. Clinical laboratory data
      will be summarized descriptively and listed by treatment group. The change from pre dose to
      the end of the study will also be summarized. Prior and concomitant medications will be coded
      with the World Health Organization Drug Dictionary and listed. Vital signs and
      electrocardiogram data will be summarized and listed by dose group and visit.
    

Intervention name(s): Doxorubicin hydrochloride liposome
Intervention type(s): Drug
Intervention description(s): 50mg/m2,IV on day1 of each cycle,On Day 1 of Cycle 2, patients will crossover to the alternate reference or test formulation,After completion of Cycle 2 (Day 28), patients will be continued on the treatment of Doxorubicin Hydrochloride Liposome Injection up to 4 more cycles if tolerance permits under guidance of their attending physicians.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment