Clinical trial NCT03794778: Evaluation of PLD Combined With Carboplatin Versus Paclitaxel Plus Carboplatin in the First-line Treatment of Epithelial Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Efficacy and Safety
Keywords: PEGylated Doxorubicin Hydrochloride Liposome Injection
Duomeisu
First-line treatment
Epithelial Ovarian Cancer
Lead sponsor: Women's Hospital School Of Medicine Zhejiang University
Sponsor class: OTHER
First posted: 2019-01-07
Enrollment: 396
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: PFS
timeFrame: 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 outcomes:
measure: OS
timeFrame: 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
measure: ORR
timeFrame: From date of randomization until PD or death from any cause, assessed up to 36 months.
measure: DCR
timeFrame: From date of randomization until PD or death from any cause, assessed up to 36 months.
measure: the incidence and severity of adverse reactions
timeFrame: 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.
measure: quality of life assessment
timeFrame: 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.
Other outcomes:
Locations:
city: Zhejiang
country: China
facility: Women's Hospital School Of Medicine Zhejiang University
state: Hangzhou
Study officials:
References: