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

Sponsor

Affiliated Cancer Hospital & Institute of Guangzhou Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03373058

Collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other), Third Affiliated Hospital, Sun Yat-Sen University (Other), Henan Provincial People's Hospital (Other), Xiangya Hospital of Central South University (Other), The Third Xiangya Hospital of Central South University (Other), Peking University Cancer Hospital & Institute (Other), Peking University People's Hospital (Other), Cancer Hospital of Guizhou Province (Other), Chinese PLA General Hospital (Other), Hebei Medical University Fourth Hospital (Other), The Second Hospital of Hebei Medical University (Other), West China Second University Hospital (Other), Peking Union Medical College Hospital (Other), First Affiliated Hospital, Sun Yat-Sen University (Other), Henan Cancer Hospital (Other), Tianjin Medical University Cancer Institute and Hospital (Other), The Third Affiliated Hospital of Guangzhou Medical University (Other), Wuhan University (Other), RenJi Hospital (Other), Obstetrics & Gynecology Hospital of Fudan University (Other), Southern Medical University, China (Other), Fourth Affiliated Hospital of Guangxi Medical University (Other), Shandong Cancer Hospital and Institute (Other), Beijing Obstetrics and Gynecology Hospital (Other), Chongqing University Cancer Hospital (Other), Xinqiao Hospital of Chongqing (Other), Wuhan Union Hospital, China (Other), First Affiliated Hospital of Chongqing Medical University (Other), Affiliated Cancer Hospital of Shantou University Medical College (Other)

310

Enrollment

Locations

Arms

44.5

Anticipated Duration (Months)

44.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma	Procedure: Hyperthermic Intraperitoneal Chemotherapy Procedure: cytoreductive surgery Drug: adjuvant chemotherapy	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

310 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 15, 2019

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group 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 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. Other Names: HIPEC Procedure: cytoreductive surgery Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration. Other Names: CRS Drug: adjuvant chemotherapy 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. Other Names: ACT
Active Comparator: Control group 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 Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration. Other Names: CRS Drug: adjuvant chemotherapy 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. Other Names: ACT

Arm

Intervention/Treatment

Experimental: Experimental group

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

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.

Other Names:

HIPEC

Procedure: cytoreductive surgery

Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration.

Other Names:

CRS

Drug: adjuvant chemotherapy

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.

Other Names:

ACT

Active Comparator: Control group

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

Cytoreductive surgery (CRS) is performed when Faggoti value is less than 6 via laparoscopic exploration.

Other Names:

CRS

Drug: adjuvant chemotherapy

Other Names:

ACT

Outcome Measures

Primary Outcome Measures

Median recurrence-free survival [3 years]
assess median recurrence-free survival during 3 years in both study arms

Secondary Outcome Measures

Median overall survival [3 years]
assess median overall survival during 3 years in both study arms
Median progression-free survival [3 years]
assess median progression-free survival during 3 years in both study arms
Risk factors for morbidity and mortality [30 days; 3 years]
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
Quality of life for ovarian cancer [3 years]
Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (QLQ-OV28)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Affiliated Tumor Hospital of Guangzhou Medical University	Guangzhou	Guangdong	China	510095
2	Sun Yat-sen Memorial Hospital,Sun Yat-sen University	Guanzhou	Guangdong	China	510235
3	Beijing Cancer Hospital	Beijing		China
4	Chongqing Cancer Hospital	Chongqing		China
5	The First Affiliated Hospital of Chongqing Medical University	Chongqing		China
6	Hubei General Hospital	Wuhan		China
7	Henan Cancer Hospital	Zhengzhou		China

Sponsors and Collaborators

Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Henan Provincial People's Hospital
Xiangya Hospital of Central South University
The Third Xiangya Hospital of Central South University
Peking University Cancer Hospital & Institute
Peking University People's Hospital
Cancer Hospital of Guizhou Province
Chinese PLA General Hospital
Hebei Medical University Fourth Hospital
The Second Hospital of Hebei Medical University
West China Second University Hospital
Peking Union Medical College Hospital
First Affiliated Hospital, Sun Yat-Sen University
Henan Cancer Hospital
Tianjin Medical University Cancer Institute and Hospital
The Third Affiliated Hospital of Guangzhou Medical University
Wuhan University
RenJi Hospital
Obstetrics & Gynecology Hospital of Fudan University
Southern Medical University, China
Fourth Affiliated Hospital of Guangxi Medical University
Shandong Cancer Hospital and Institute
Beijing Obstetrics and Gynecology Hospital
Chongqing University Cancer Hospital
Xinqiao Hospital of Chongqing
Wuhan Union Hospital, China
First Affiliated Hospital of Chongqing Medical University
Affiliated Cancer Hospital of Shantou University Medical College

Investigators

Study Director: Shuzhong Cui, M.D, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Study Director: Zhongqiu Lin, M.D, Sun Yat-sen Memorial Hospital,Sun Yat-sen University