Efficacy of HIPEC in the Treatment of Advanced-Stage Epithelial Ovarian Cancer After Cytoreductive Surgery

Study Overview
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Brief Summary
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This project is a multi-center, prospective, randomized controlled clinical observation the safety and efficacy of hyperthermic intraperitoneal chemotherapy in the treatment of advanced-stage epithelial ovarian cancer after cytoreductive surgery. Median recurrence-free survival is the primary end points of this project.

Detailed Description
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The current standard treatment for epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer is maximal cytoreductive surgery followed by intravenous chemotherapy with or without intraperitoneal chemotherapy (IP). Recently, the organizations of SGO and ASCO recommended that women with Fagotti score by laparoscopic exploration < 6 would benefit from primary cytoreductive surgery followed by postoperative chemotherapy, and are likely to attain optimal cytoreduction (residual lesion ≤ 1 cm). Hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, hyperthermic intraperitoneal chemotherapy (HIPEC) as newly postoperative chemotherapy after primary cytoreductive surgery in the treatment of ovarian cancer could lead to higher response rate and better survival outcomes.

Official Title
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A Phase III Multicenter Prospective Randomized Controlled Clinical Trial of Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Advanced-Stage Epithelial Ovarian Cancer After Cytoreductive Surgery

Conditions
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Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Procedure: Hyperthermic Intraperitoneal Chemotherapy
* Procedure: cytoreductive surgery
* Drug: adjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease status primary epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer (Stage III ) Fagotti score by laparoscopic exploration < 6 Residual tumor < 1cm after completion of cytoreductive surgery 18 < Age < 70 year old Expected survival > 3 months Performance status: ECOG 0-1 Adequate bone marrow function Hb ≥8 g/dl (After correction in case of iron deficient anemia) WBC ≥ 3,000/mm3, Platelet ≥ 100,000/mm3 Adequate renal function Creatinine ≤ 1.5 mg/dl, and adequate hepatic function Bilirubin ≤ 1.5 mg/dl and AST and ALT ≤ 80 IU/L Voluntary participation after getting written informed consent. Exclusion Criteria: Fagotti score by laparoscopic exploration >= 6 Suboptimal debulking (residual tumor > 1cm) Extensive adhesion in peritoneal cavity Previous History of other malignancies (except excision of skin cancer, thyroid cancer) Poorly controlled disease e.g. atrial fibrillation, stenocardia, cardiac insufficiency, persistent hypertension despite medicinal treatment, ejection fraction<50% Receiving other chemotherapy, radiotherapy or immunotherapy Patients who are unsuitable candidates by doctor's decision Without given written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Experimental group<br>Cytoreductive surgery Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Docetaxel 75 mg/m^2 and cisplatin 75 mg/m^2 intraperitoneally in succession 6 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour(Docetaxel 75 mg/m^2, if paclitaxel is not available.)+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks. | Procedure: Hyperthermic Intraperitoneal Chemotherapy<br>* HIPEC is performed as postoperative chemotherapy after cytoreductive surgery for advanced-stage epithelial ovarian cancer. The first HIPEC is conducted within 48h after cytoreductive surgery: Paclitaxel 175 mg/m^2, 43°C, 90min. The second HIPEC is performed after 48 hours of the first HIPEC. The HIPEC regimens are Docetaxel 75 mg/m^2 and cisplatin 75 mg/m^2, respectively, 43°C, 90min.<br>* Other names: HIPEC;Procedure: cytoreductive surgery<br>* Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration.<br>* Other names: CRS;Drug: adjuvant chemotherapy<br>* Systemic chemotherapy regimens after HIPEC treatment are paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks for 2 cycles in experimental group. Systemic chemotherapy regimens after IDS are paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks for 3 cycles in control group.<br>* Other names: ACT;|
| Active Comparator: Control group<br>Cytoreductive surgery 6 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour(Docetaxel 75 mg/m^2, if paclitaxel is not available)+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks. | Procedure: cytoreductive surgery<br>* Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration.<br>* Other names: CRS;Drug: adjuvant chemotherapy<br>* Systemic chemotherapy regimens after HIPEC treatment are paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks for 2 cycles in experimental group. Systemic chemotherapy regimens after IDS are paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks for 3 cycles in control group.<br>* Other names: ACT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median recurrence-free survival | assess median recurrence-free survival during 3 years in both study arms | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival | assess median overall survival during 3 years in both study arms | 3 years | 
| Median progression-free survival | assess median progression-free survival during 3 years in both study arms | 3 years | 
| Risk factors for morbidity and mortality | The early complication and mortality are defined as the event observed within 30 days after intervention, while the time frame for late complication is the period beyond 30 days after intervention to the end of 3 years. Complications are ranked from grade 0-5 according to CTCAE V4.0 | 30 days; 3 years | 
| Quality of life for ovarian cancer | Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (QLQ-OV28) | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperthermic Intraperitoneal Chemotherapy, Advanced-Stage Epithelial Ovarian Cancer, Cytoreductive surgery, Postoperative Chemotherapy