Hyperthermic Intraperitoneal Chemotherapy, Neoadjuvant Chemotherapy
Conditions
Keywords
HIPEC, Neoadjuvant chemotherapy, High-grade serous ovarian cancer
Brief summary
Background: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. Methods: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events.
Interventions
PROCEDUREHIPEC
Docetaxel (60-75mg/m2) perfusion solution will be infused into the peritoneal cavity through the tubes within 24 hours after the laparoscopic evaluation. Then, perfusate containing cisplatin (75 mg/m2) will be infused 24 hours later. NHIPEC will be administered at 43°C for a duration of 60min. Saline solution (3000mL) will be used to dissolve the drug, and it will be heated and circulated at a flow rate of 300-500 mL/min.
PROCEDUREintravenous chemotherapy
Patients in the control group will receive three cycles of intravenous NACT. The regimen of intravenous NACT is docetaxel 60-75mg/m2 followed by carboplatin AUC 5 for a 21-day cycle.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
All tissue samples harvested during IDS will be subjected to H&E expert pathological evaluation to confirm the diagnosis of high-grade serous ovarian cancer(HGSOC). Omental slides will be independently reviewed by two pathologists to determine those with the greatest amount of viable tumour, and one slide of each site will be selected. The two pathologists, who will be blinded to the written report and each other's results, will independently score each slide according to the CRS system.
Intervention model description
The eligible patients will be randomised into an experimental group (NHIPEC +intravenous NACT) or a control group (intravenous NACT). Patients in the NHIPEC experimental group will receive NHIPEC and two cycles of intravenous NACT, while patients in the control group will receive three cycles of intravenous NACT. All patients will undergo IDS within 4weeks after the last cycle of NACT.
Eligibility
Sex/Gender
FEMALE
Age
17 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. International Federation of Gynecology and Obstetrics(FIGO) stage IIIC-IVA, HGSOC 2. Patients with Fagotti score ≥8 3. Adequate kidney function (blood creatinine 58-96 µmol/L) 4. Adequate haematological function (haemoglobin ≥110g/L, leucocytes ≥4.0×109/L, neutrophils ≥2.0×109/L, platelets≥100×109/L) 5. Adequate liver function (serum total bilirubin 3.4-22.2µmol/L, alanine aminotransferase (ALT) 7-40U/L, aspartate aminotransferase (AST) 13-35U/L, AST/ALT ≤1.5) 6. World Health Organization(WHO) score 0-2
Exclusion criteria
1. Patients who had received chemotherapy, radiotherapy or any kind of targeted therapy. 2. Patients with complete intestine obstruction. 3. Expected life span ≤8 weeks. 4. Complicated with any other known malignancies. 5. Patients with poor cardiopulmonary function, which would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| chemotherapy response score(CRS) 3 | At the end of cycle 3 NACT (each cycle is 21 days) | the proportion of chemotherapy response score 3, which means a better outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NHIPEC-related adverse effects | during the procedure | the adverse effects of NHIPEC |
| progression-free survival(PFS) | From date of randomization until the date of first documented progression, assessed up to 3 years | progression-free survival |
| overall survival(OS) | From date of randomization until the time of death from any cause, assessed up to 3 years | overall survival |
| Rate of R0 resection | At the end of cycle 3 NACT (each cycle is 21 days),when IDS is conducted | the R0 resection rate of interval debulking surgery(IDS) |
Countries
China
Contacts
Primary Contactmiaofang Wu, Doctor
Outcome results
None listed