Apatinib and Etoposide Capsule Versus Weekly Paclitaxel in Patients With Platinum Resistant Ovarian Cancer

Study Overview
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Brief Summary
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The study is conducted to evaluate the efficacy, safety and tolerability of apatinib (375 mg qd) and etoposide capsule (50 mg/d, d1-14, q3w) in subjects with platinum resistant or refractory ovarian cancer compared with weekly paclitaxel (80 mg/m2, d1, d8, d15, q3w).

Official Title
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AMELIE: A Phase 3 Randomized, Open-label, Multicenter Trial of Apatinib and Etoposide Capsule Versus Weekly Paclitaxel in Patients With Platinum Resistant or Refractory Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Apatinib
* Drug: Etoposide
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 Years and older Epithelial ovarian, fallopian tube or primary peritoneal cancer Platinum refractory and resistant disease (disease progression during platinum therapy or within 6 months of platinum therapy) EOCG performance status of 0-1 Exclusion Criteria: Uncontrolled hypertension ( systolic ≥140 mmHg or diastolic ≥90 mmHg despite antihypertensive therapy) Known hypersensitivity to any of the study drugs or excipients. Known hereditary or acquired bleeding and thrombotic tendencies (e.g. hemophiliacs, coagulation disorders, thrombocytopenia, etc.); Congenital or acquired immune deficiency (e.g. HIV infected)

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib and Etoposide capsule<br>Apatinib (375 mg qd, q3w) and Etoposide capsule(50 mg/d, d1-14, q3w) combination until disease progression or intolerable toxicity | Drug: Apatinib<br>* Subjects receive Apatinib orally, Dosage form: tablet, Strength: 375 mg/d<br>Drug: Etoposide<br>* Subjects receive Etoposide capsule orally, d1-14, q3w, Dosage form: capsule, Strength: 50 mg/d<br>|
| Active Comparator: Weekly Paclitaxel<br>Weekly Paclitaxel (80 mg/m2, d1, d8, d15, q3w) until disease progression or intolerable toxicity | Drug: Paclitaxel<br>* Subjects receive Weekly Paclitaxel, intravenously, d1, d8, d15, q3w, Dosage form: injectable, Strength: 80 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) by independent review committee(IRC) | PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the IRC according to the RECIST criteria | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | Frequency and severity of Adverse Events or Serious Adverse Events as defined by CTCAE version 5.0 | up to approximately 2 years | 
| PFS by investigator | PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigator according to the RECIST criteria | up to approximately 2 years | 
| Objective Response Rate (ORR) | Proportion of subjects who have a complete or partial response relative to baseline as assessed per RECIST 1.1 criteria as well as Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)-125 criteria. | up to approximately 2 years | 
| Overall Survival (OS) | OS is the time interval from the date of randomization to death from any cause. | up to approximately 3 years | 
| EQ-5D-5L questionnaire | EQ-5D-5L is a questionnaire that focus on issues specific to ovarian cancer. | up to approximately 2 years | 
| FOSI-8 questionnaire | FOSI-8 is a questionnaire that focus on issues specific to ovarian cancer. | up to approximately 2 years |