Phase 2 AMG 386 in Comb. Paclitaxel for Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer
Condition: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
MeSH terms: Fallopian Tube Neoplasms; Peritoneal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is a phase 2, randomized, double-blind, placebo controlled, multi-center study to
      estimate the improvement in PFS (compared to control subjects) and evaluate the safety and
      tolerability of AMG 386 in combination with paclitaxel in the treatment of subjects with
      advanced recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

      Primary Outcome Measure:

      • Progression free survival (PFS)

      Secondary Outcome Measures:

        -  Object Response Rate (ORR), duration of response (DOR). CA-125 response rate

        -  Safety and Tolerability

        -  Change and duration of change on blood levels of CA-125
    

Detailed description: 
      Primary Objective:

      To estimate the treatment effect as measured by progression free survival (PFS) of subjects
      with recurrent ovarian cancer receiving AMG 386 (either 3 mg/kg or 10 mg/kg IV QW) in
      combination with paclitaxel (80 mg/m2 IV QW; 3 on/1 off)compared to subjects receiving
      paclitaxel (80 mg/m2 IV QW; 3 on/1 off) plus placebo

      Secondary Objective(s):

        -  To evaluate the safety and tolerability of the combination regimen of AMG 386/paclitaxel

        -  To estimate other measures of treatment effect (by parameters other than PFS) of
           subjects receiving AMG 386 in combination with paclitaxel compared to subjects receiving
           paclitaxel plus placebo

        -  To evaluate the AMG 386 pharmacokinetics parameters (Cmax and Cmin ) when administered
           with paclitaxel in subjects with recurrent ovarian cancer

        -  To estimate the incidence of occurrence of anti-AMG 386 antibody formation

        -  To estimate the change and duration of change on blood levels of CA-125

        -  To evaluate the clinical benefit among subjects receiving AMG 386 10 mg/kg monotherapy
           after disease progression on paclitaxel

        -  To estimate the impact of AMG 386 on patient reported ovarian cancer specific symptoms
           and HRQoL using the FACT-O, the FACT-O ovarian cancer subscale (OCS), and the FACT-O
           3-item (O1, O2, O3) cancer symptom specific subscale (OCS 3-item subscale)

      Exploratory Objective(s):

        -  To explore the associations between progression free survival, objective response,
           CA-125, and continuous measures of tumor burden (the percentage change from baseline in
           the sum of the longest diameters of target lesions)

        -  To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of
           angiogenic cytokines, tumor apoptosis, CA-125 and other markers

        -  To investigate the effects of genetic variation in drug metabolism, cancer genes and
           drug target genes on ovarian cancer and subject response to investigational product
           (separate informed consent)

        -  To explore the impact of AMG 386 on patient reported overall health status as measured
           by the EuroQoL (EQ-5D)

      Hypothesis:

      This study will provide an estimate and corresponding 2-sided 80% confidence interval with an
      approximate maximum half-width of 0.22 of the efficacy, as measured by the PFS hazard ratio
      of AMG 386 in combination with paclitaxel versus paclitaxel alone for 2 pooled dose groups of
      AMG 386 (10 mg/kg QW and 3 mg/kg QW) in combination with paclitaxel versus the paclitaxel
      plus placebo group.
    

Intervention name(s): AMG 386; AMG 386; Paclitaxel; AMG 386 Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 10mg/kg; 3 mg/kg; Paclitaxel 80 mg/m2 IV QW (3 on/1 off); AMG 386 Placebo
Intervention MeSH terms: Paclitaxel; Trebananib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Advanced Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer