Evaluation of PLD Combined With Carboplatin Versus Paclitaxel Plus Carboplatin in the First-line Treatment of Epithelial Ovarian Cancer

Study Overview
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Brief Summary
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This is a randomized, multicenter, open, controlled Post-Marketing Study. 396 patients who were histopathology or exfoliated cell pathology of pleural and ascites confirmed with epithelial ovarian cancer/fallopian tube/peritoneal cancer were enrolled in this study. The subjects will be randomly assigned to one of the two treatment groups at a 1: 1 ratio, and the stratification factors included: chemotherapy type (adjuvant chemotherapy/neoadjuvant chemotherapy), residual disease after surgery (>1cm, <1cm, no primary surgery), stage (Ic, II, III or IV), pathological typing, Eastern Cooperative Oncology Group performance status (0 to 1 or 2), BRCA1/2 gene mutation.

Detailed Description
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Subjects will receive one of two treatment regimens: Group A: intravenous infusion of liposomal doxorubicin 30 mg/m2, d1; carboplatin AUC 5 (dosed according to the Calvert formula, with creatinine clearance estimated according to the Cockcroftformula), intravenous infusion, d1; once every 21days, 3 6 cycles for early stage patients and 6 cycles for late stage. Group B: intravenous infusion of paclitaxel 175 mg/m2, d1; carboplatin AUC 5, intravenous infusion, d1; once every 21days, 3 6 cycles for early stage patients and 6 cycles for late stage. Treatment was initially administered for three cycles, and patients with stable or responding disease continued treatment for further a three cycles. The main purpose is to evaluate the efficacy and safety of liposomal doxorubicin plus carboplatin in the first-line treatment of epithelial ovarian cancer. The primary endpoint is progression free survival (PFS), the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR):CR+PR+SD, the incidence and severity of adverse reactions and health-related quality of life (HQL) assessment.

Official Title
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Evaluation of PEGylated Doxorubicin Hydrochloride Liposome Injection(Duomeisu®) Combined With Carboplatin Versus Paclitaxel Plus Carboplatin in the First-line Treatment of Epithelial Ovarian Cancer: A Randomized, Open, Multicenter Clinical Study

Conditions
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Efficacy and Safety

Intervention / Treatment
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* Drug: pegylated liposomal doxorubicin
* Drug: paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75years old; Histopathologically or exfoliated cell pathology of pleural and ascites confirmed with epithelial ovarian cancer/fallopian tube/peritoneal cancer; According to the International Federation of Obstetrics and Gynecology (FIGO), the stage is Ic-IV; Imaging assessment is based on the solid tumor efficacy evaluation standard (RECIST) version 1.1, lesions can be measured, or patients' CA125 assessed according to GCIG criteria; Neoadjuvant chemotherapy can be given to patients with excessive tumor volume or a wide range of lesions, who are not expected to achieve ideal cytoreductions before surgery; ECOG score ≤ 2; Expected survival time ≥ 3 months; LVEF ≥ 50%; Bone Marrow Function: ANC：≥1.5×109/L； PLT：≥100×109/L；Hb: ≥90g/L; Liver and renal function:Serum creatinine ≤ normal upper limit (ULN) 1.5times; aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤ULN 2.5times, or <ULN 5times in the presence of liver metastasis; total bilirubin (TBil) level≤ ULN 1.5 times, or ≤ ULN 2.5times if Gilbert's syndrome are present; The childbearing age subjects must agree to take effective contraceptive measures during the trial; the serum or urine pregnancy test must be negative, non-lactating; Signed the informed consent. Exclusion Criteria: Patients with low-grade malignant potential ovarian tumors; Patients who had previously received chemotherapy or pelvic and abdominal radiotherapy; Patients planning to receive abdominal or pelvic chemotherapy; The New York Heart Association (NYHA) graded class II heart disease patients (including grade II) previous or current; Other malignant tumors have been found in the past 5 years,except for cured cervical carcinoma in situ, non melanoma of the skin; Uncontrolled systemic infection requiring anti-infective treatment; Allergies to chemotherapeutic drugs or their excipients or intolerant patients; Subjects with ≥2 grade peripheral neuropathy according to CTCAE V 4.03; Researchers think it is not suitable for enrolling.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: study group<br>pegylated liposomal doxorubicin 30 mg/m2, i.v.,d1; carboplatin AUC 5,i.v.,d1; once every 21days, 3 6 cycles for early stage patients and 6 cycles for late stage. | Drug: pegylated liposomal doxorubicin<br>* PLD 30 mg/m2, i.v.,d1; once every 21days<br>* Other names: duomeisu;Drug: Carboplatin<br>* carboplatin AUC 5, i.v.,d1; once every 21days,<br>* Other names: kabo;|
| Active Comparator: chemotherapy<br>paclitaxel 175 mg/m2, i.v.,d1; carboplatin AUC 5, i.v.,d1; once every 21days, 3 6 cycles for early stage patients and 6 cycles for late stage. | Drug: paclitaxel<br>* paclitaxel 175 mg/m2, i.v.,d1; once every 21days<br>* Other names: zishanchun;Drug: Carboplatin<br>* carboplatin AUC 5, i.v.,d1; once every 21days,<br>* Other names: kabo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. | From date of randomization until the date of first documented progression or death from any cause, whichever occurred first, or last follow-up for patients alive without progression, assessed up to approximately 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | overall survival | From date of randomization until the date of death from any cause, or date of last follow-up for patients still alive, assessed up to 36 months | 
| ORR | ORR is defined as the rate of CR or PR, as determined by IRC using RECIST v1.1 criteria among patients with at least one target lesion. Activity was also described in women with nontarget lesions only and in women without any tumor lesion but with elevated CA-125 levels before starting treatment. | From date of randomization until PD or death from any cause, assessed up to 36 months. | 
| DCR | DCR is defined as the rate of of CR, PR, or stable disease according to RECIST v1.1. | From date of randomization until PD or death from any cause, assessed up to 36 months. | 
| the incidence and severity of adverse reactions | Evaluate the adverse reactions rate of drugs assessed by number and severity of adverse events in the treatment. | A summary of adverse events of each cycle,from date of administration of drugs until 30 days after the last chemotherapy or progression,whichever came first,assessed up to 36 months. | 
| quality of life assessment | according to the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30).The basic content of life quality assessment includes: physical health, mental health, social function, disease status and overall health perception. | It will be assessed at baseline and before the administration of drugs at each first day of every two chemotherapy cycles, up to 6 cycles,each cycle is 21 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PEGylated Doxorubicin Hydrochloride Liposome Injection, Duomeisu, First-line treatment, Epithelial Ovarian Cancer