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

Phase 3
Conditions
Fallopian Tube Cancer
Epithelial Ovarian Cancer
Primary Peritoneal Carcinoma
Interventions
Procedure: Hyperthermic Intraperitoneal Chemotherapy
Procedure: Interval debulking surgery
Drug: neoadjuvant chemotherapy
Drug: adjuvant chemotherapy
Registration Number
NCT03180177
Lead Sponsor
Shu-Zhong Cui
Brief Summary

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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
263
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental groupHyperthermic Intraperitoneal Chemotherapy1. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 2. 2 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 3. Interval debulking surgery 4. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 5. 2 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Experimental groupInterval debulking surgery1. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 2. 2 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 3. Interval debulking surgery 4. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 5. 2 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Experimental groupneoadjuvant chemotherapy1. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 2. 2 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 3. Interval debulking surgery 4. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 5. 2 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Experimental groupadjuvant chemotherapy1. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 2. 2 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 3. Interval debulking surgery 4. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2 intraperitoneally in succession 5. 2 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Control groupInterval debulking surgery1. 3 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 2. Interval debulking surgery 3. 3 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Control groupneoadjuvant chemotherapy1. 3 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 2. Interval debulking surgery 3. 3 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Control groupadjuvant chemotherapy1. 3 cycles of neoadjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks 2. Interval debulking surgery 3. 3 cycles of adjuvant chemotherapy: paclitaxel 175 mg/m\^2 IV\>3 hour+ carboplatin AUC = 5-6 IV\>1 hour, every 3 weeks
Primary Outcome Measures
NameTimeMethod
Percentage of optimal debulking surgeryThrough study completion, an average of 1 year

evaluate the percentage of optimal debulk (residual disease \< 1cm) after interval debulking surgery between study arms

PR/SD rateThrough study completion, an average of 1 year

calculate the percent of partial remission (PR) plus stable disease (SD) of patients received HIPEC+NACT or NACT alone in both two arms

Disease-free survival rate3 years

assess disease free survival rate during 3 years in both study arms

Secondary Outcome Measures
NameTimeMethod
Overall survival rate3 years

assess overall survival rate during 3 years in both study arms

Risk factors for morbidity and mortalityThrough study completion, an average of 1 year

determine percent of patients wtih Grade I-IV adverse events according to NCI criteria, Common Terminology Criteria for AE (CTCAE 4.0).

Quality of life3 years

Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30)

Quality of life for ovarian cancer3 years

Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (QLQ-OV28)

Trial Locations

Locations (1)

Department of Abdominal Surgery (Section 2), Affiliated Tumor Hospital of Guangzhou Medical University

🇨🇳

Guangzhou, Guangdong, China

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