A Randomized Prospective Trail of HIPEC in Recurrent Ovarian Cancer Patients With HRR Mutation

Study Overview
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Brief Summary
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A phase III prospective study with the primary objective to investigate the benefit of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in ovarian cancer patients with mutations in homologous recombination repair (HRR) genes. The target population for this study is patients with recurrent ovarian, peritoneal or fallopian tube cancers undergoing Cytoreductive Surgery (CRS). Patients will be divided into two groups according to HRR genes mutation, each group will be further divided into two sub-groups with different intervention. Patients in Group A are HRR mutated type, sub-group 1 will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group 2 will undergo CRS and then go on to intravenous chemotherapy. Patients in Group B are HRR wild type, sub-group 3 will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group 4 will undergo CRS and then go on to intravenous chemotherapy. All patients will receive maintenance therapy with Niraparib after primary treatment. Prognostic information will be collected for investigation of survival benefits of patients.

Official Title
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A Randomized Prospective Trail of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Recurrent Ovarian Cancer Patients With Mutations in Homologous Recombination Repair (HRR) Genes

Conditions
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Ovarian Cancer, Epithelial Ovarian Cancer, Ovarian Cancer, Epithelial, Hyperthermic Intraperitoneal Chemotherapy(HIPEC), Homologous Recombination Repair Gene Mutation

Intervention / Treatment
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* Procedure: CRS+HIPEC
* Procedure: CRS alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-75 Karnofsky performance status >50 or World Health Organization performance score < 2 primary or recurrence ovarian, peritoneal or fallopian tube epithelial cancer; first intra-abdominal recurrence without distant metastasis (including: unique resectable pleural metastasis which are platinum-sensitive; resectable single lymphatic metastasis retroperitoneal or inguinal) preoperative platinum-based chemotherapy (carboplatin and paclitaxel, carboplatin and liposomal doxorubicin, gemcitabine, trabectedin or topotecan) lesion can be removed completely or residual disease < 0.5 cm last chemotherapy finished no more than 12 weeks after surgery no hepatic function damage white blood cell count ≥3.5*10^9/L; platelet count ≥80*10^9/L; Hemoglobin ≥90g/L no contraindication of surgery and anesthesia life expectancy ≥ 3 months informed consent form signed Exclusion Criteria: age < 18 or >75 no history of other cancer platinum allergy distant metastasis used anti-angiogenic drug within 8 weeks possibility of more than two resection of alimentary canal recurrence < 6 months after primary treatment histologic type: non epithelial origin infection out of control follow-up unable to carry on (geographic or psychic) cardiac insufficiency or respiratory insufficiency has received HIPEC already being in other clinical study pregnancy or lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRR mt 1<br>Patients are HRR mutated type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy. | Procedure: CRS+HIPEC<br>* Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy. A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.<br>|
| Experimental: HRR mt 2<br>Patients are HRR mutated type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy. | Procedure: CRS alone<br>* Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.<br>|
| Experimental: HRR wt 3<br>Patients are HRR wild type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy. | Procedure: CRS+HIPEC<br>* Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy. A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.<br>|
| Experimental: HRR wt 4<br>Patients are HRR wild type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy. | Procedure: CRS alone<br>* Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | The progression-free survival interval was the time between diagnosis and evidence of recurrent or progressive disease. | up to 36 months since diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The overall survival interval was the time between diagnosis and death or last follow-up. | up to 36 months since histological diagnosis | 
| DP9 | The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 9 months since histological diagnosis. | the 1 day of histological diagnosis and 9 months after | 
| DP12 | The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 12 months since histological diagnosis. | the 1 day of histological diagnosis and 12 months after | 
| Serious adverse events, SAEs | Serious adverse events occur within 30 days after surgery, measured with CTCAE 4.0 | surgery and with in 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Homologous Recombination Repair Gene Mutation, hyperthermic intraperitoneal chemotherapy, Epithelial Ovarian Cancer