Efficacy and Safety of Apatinib As Third Line Therapy in Patients With Advanced Ovarian Cancer

Study Overview
=================
Brief Summary
-----------------
The study is to investigate the efficacy and safety of apatinib in patients with advanced ovarian cancer,who has received second-line chemotherapy and failed.

Detailed Description
-----------------
Ovarian cancer is the third most common gynecological malignancy，just less than endometrial cancer and cervical cancer. Because most patients with advanced ovarian cancer can not get the ideal tumor cell reduction surgery, and multi-drug resistance often emerges after repeated chemotherapy，recurrent and metastatic ovarian cancer has become one of the major diseases that threaten women's health. There is strongly necessary to explore effective therapeutic drugs and means to improve prognosis of these patients and improve the quality of life. The study，as a double blind clinical trial ,is to investigate the efficacy and safety of apatinib in patients with advanced ovarian cancer,who has received second-line chemotherapy regimens and failed. A total of 60 patients with performance status 0-2 were enrolled in this study, and were randomly divided into two groups--one group of 40 patients receiving apatinib，and another of 20 patients receiving placebo.

Official Title
-----------------
Efficacy and Safety of Apatinib As Third Line Therapy in Patients With Advanced Ovarian Cancer

Conditions
-----------------
Angiogenesis Inhibitors，Ovarian Neoplasms

Intervention / Treatment
-----------------
* Drug: apatinib
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years to 70 years; Had a histologically or cytologically confirmed diagnosis of epithelial ovarian cancer； unfit for radical surgery and had received second-line chemotherapy，the disease still progressed or can not tolerate the chemotherapy; Had a disease status that was measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST, version1.1); Had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2; Had a life expectancy of at least 12 weeks; Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥90g/L, platelets ≥ 80×10^9/L, neutrophils ≥ 1.5×10^9/L, total bilirubin within 1.5×the upper limit of normal (ULN), and b) ALT and AST≤2.5×the ULN (If liver metastases, serum creatine ≤ 1.5 x ULN); Had not gastrointestinal diseases that lead to malabsorption or impact Drug absorption; had good compliance; Signed and dated informed consent. Exclusion Criteria: patients who had received anti-vascular therapy; Allergic to any ingredients of Apatinib; Participated in other drug clinical researchers within four weeks; Have a variety of factors that affect oral medication (such as can not swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.) Severe infection; Patients with serious cardiovascular diseases,such as unstable angina, grade 3-4 heart dysfunction (NYHA Standard), congestive heart failure, poor-controlled arterial hypertension despite standard medical management; Patients who received major surgical operations within 4 weeks before screening; Patients who manifested arterial/venous thrombus events, e.g.cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening; Past or concurrent with other malignancies, except for cured skin basal cell carcinoma and cervical in situ cancer; Have a history of psychiatric abuse and can not quit or have mental disorders.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>apatinib 500 mg p.o. once daily | Drug: apatinib<br>* Patients in experimental group will take 500mg apatinib daily orally，and patients in control group will take placebo<br>|
| Placebo Comparator: control group<br>placebo p.o. once daily | Drug: Placebos<br>* Physical properties of placebos are consistent with apatinib<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Time from randomization until disease progression or death | approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Time from randomization until death from any cause of death | approximately 2 years | 
| Objective response rate (ORR) | Proportion of patients with reduction in tumor burden of a predefined amount | approximately 2 years | 
| disease control rate (DCR) | the total proportion of patients who demonstrate a response to treatment | approximately 2 years | 
| Quality of life (QoL) | As measured by the European Organization for Research and Treatment of Cancer questionnaire (EORTC QLQ C30) | approximately 2 years |