AMG 386 (Trebananib) in Ovarian Cancer (TRINOVA-2)

Study Overview
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Brief Summary
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To determine if AMG 386 plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival (PFS) The hypothesis for this study is that AMG 386 plus PLD will prolong PFS compared to placebo plus PLD in women with recurrent partially platinum sensitive or resistant epithelial ovarian, primary peritoneal or fallopian tube cancer.

Official Title
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A Phase 3, Randomized, Double-Blind Trial of Pegylated Liposomal Doxorubicin (PLD) Plus AMG 386 or Placebo in Women With Recurrent Partially Platinum Sensitive or Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer

Intervention / Treatment
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* Drug: AMG386 plus PLD
* Drug: Placebo plus PLD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer Radiographically documented disease progression either on or following the last dose of the prior regimen for epithelial ovarian, primary peritoneal, or fallopian tube cancer Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. Female 18 years of age or older at the time the written informed consent is obtained Adequate organ and hematological function Exclusion Criteria: Subjects who have received more than 3 previous regimens of anti cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer Subjects treated with prior pegylated liposomal doxorubicin (PLD) or any anthracycline-based or mitoxantrone-based chemotherapy Subjects with primary platinum-refractory disease Subjects with platinum-free interval (PFI) > 12 months from their last platinum based therapy History of central nervous system metastasis Major surgery within 28 days prior to randomization or still recovering from prior surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo plus PLD<br>Arm B: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW) | Drug: Placebo plus PLD<br>* Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW)<br>|
| Experimental: AMG386 plus PLD<br>Arm A: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW) | Drug: AMG386 plus PLD<br>* AMG 386 is a first in class investigational anti angiogenic drug that provides potent and selective inhibition of angiopoietins. AMG 386 is designed to inhibit angiogenesis by sequestering Ang1 and Ang2, thereby preventing their interaction with the Tie2 receptor. Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by progression-free survival, defined as the time from randomization to the earliest of the dates of first radiologic disease progression per RECIST 1.1 with modifications |  | Radiological imaging will be performed 8 weeks ± 1 week, starting from date of randomization for the first 64 weeks, then every 16 weeks ± 1 week for the next 32 weeks, and then every 24 weeks ± 4 weeks thereafter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by overall survival |  | weekly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent epithelial ovarian cancer, Fallopian tube cancer, Primary peritoneal cancer, AMG386, Pegylated Liposomal Doxorubicin