Efficacy of HIPEC as NACT and Postoperative Chemotherapy in the Treatment of Advanced-Stage Epithelial Ovarian Cancer (EHNPCTASEOC)

A Phase III Multicenter Prospective Randomized Controlled Clinical Trial of HIPEC as NACT and Postoperative Chemotherapy After Interval Debulking Surgery in the Treatment of Advanced-Stage Epithelial Ovarian Cancer

This project is a multi-center, prospective, randomized controlled clinical observation the safety and efficacy of hyperthermic intraperitoneal chemotherapy as neoadjuvant chemotherapy(NACT) and postoperative chemotherapy after interval debulking surgery (IDS) for advanced-stage epithelial ovarian cancer . PR/SD rate, percentage of optimal debulking surgery and 3-year disease-free survival is the primary end points of this project.

Study Overview

• Status: Unknown
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Procedure: Hyperthermic Intraperitoneal Chemotherapy; Procedure: Interval debulking surgery; Drug: neoadjuvant chemotherapy; Drug: adjuvant chemotherapy

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 a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to novisible disease) should receive neoadjuvant chemotherapy.

Hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, hyperthermic intraperitoneal chemotherapy (HIPEC) as neoadjuvant chemotherapy and postoperative chemotherapy after interval debulking surgery in the treatment of ovarian cancer could lead to higher response rate and better survival outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510095
      • Department of Abdominal Surgery (Section 2), Affiliated Tumor Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Disease status primary epithelial ovarian cancer, tubal cancer, and primary peritoneal cancer (Stage III and IV)
• Fagotti score by laparoscopic exploration >= 6
• After receiving HIPEC+neoadjuvant chemotherapy (NACT) or NACT alone, the curative effects evaluated according to RICIST criteria is partial remission (PR) and stable disease (SD).
• Residual tumor < 1cm after completion of interval debulking 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
• After receiving HIPEC+neoadjuvant chemotherapy (NACT) or NACT alone, the progression of disease (PD) is evaluated by doctor.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 intraperitoneally in succession; 2 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks; Interval debulking surgery; Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 intraperitoneally in succession; 2 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks	Procedure: Hyperthermic Intraperitoneal Chemotherapy; HIPEC is performed as neoadjuvant chemotherapy(NACT) and postoperative chemotherapy after interval debulking surgery (IDS) for advanced-stage epithelial ovarian cancer. The first HIPEC is conducted within 24h after laparoscopic exploration or Interval debulking surgery: Paclitaxel 175 mg/m^2, 43°C, 90min. The second HIPEC is performed after 48 hours of the first HIPEC. The second HIPEC regimens are cisplatin 75 mg/m^2, 43°C, 90min.; Other Names: HIPEC; Procedure: Interval debulking surgery; Cytoreductive surgery (CRS) is performed after neoadjuvant chemotherapy.; Other Names: IDS; Drug: neoadjuvant 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 laparoscopic exploration 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: NACT; 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; 3 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks; Interval debulking surgery; 3 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m^2 IV>3 hour+ carboplatin AUC = 5-6 IV>1 hour, every 3 weeks	Procedure: Interval debulking surgery; Cytoreductive surgery (CRS) is performed after neoadjuvant chemotherapy.; Other Names: IDS; Drug: neoadjuvant 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 laparoscopic exploration 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: NACT; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PR/SD rate	calculate the percent of partial remission (PR) plus stable disease (SD) of patients received HIPEC+NACT or NACT alone in both two arms	Through study completion, an average of 1 year
Percentage of optimal debulking surgery	evaluate the percentage of optimal debulk (residual disease < 1cm) after interval debulking surgery between study arms	Through study completion, an average of 1 year
Disease-free survival rate	assess disease free survival rate during 3 years in both study arms	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	assess overall survival rate during 3 years in both study arms	3 years
Risk factors for morbidity and mortality	determine percent of patients wtih Grade I-IV adverse events according to NCI criteria, Common Terminology Criteria for AE (CTCAE 4.0).	Through study completion, an average of 1 year
Quality of life	Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30)	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2018
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): January 24, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Hyperthermic Intraperitoneal Chemotherapy; Neoadjuvant Chemotherapy; Interval Debulking Surgery; Postoperative Chemotherapy; Advanced-Stage Epithelial Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: HIPEC-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No