Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Ovarian Cancer

Study Overview
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Brief Summary
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The current standard treatment for ovarian cancer, tubal cancer, and primary peritoneal cancer is maximal cytoreductive surgery followed by chemotherapy. Recent randomized trials of Gynecologic Oncology Group (GOG) revealed the survival gain in intraperitoneal chemotherapy compared to the intravenous chemotherapy after the optimal cytoreduction in ovarian cancer (GOG#104, GOG#114, GOG#172). Experts attributed such survival gain to the earlier cycles of intraperitoneal chemotherapy when adhesion was minimal from extensive cytoreductive procedures. Hyperthermia has an anti-cancer activity itself. Especially, hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, the combination of intraperitoneal chemotherapy with hyperthermia theoretically could lead to higher response rate and better survival outcomes. *HIPEC: hyperthermic intraperitoneal chemotherapy There will be an interim analysis when 50% of patients are enrolled. At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

Detailed Description
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If a patient is allocated to operation to remove ovarian cancer and metastatic disease in the abdomen, this trial could be considered. Before operation, laboratory test results, image result, patient's medical history, and baseline quality of life will be checked and reviewed. When optimal cytoreduction (residual tumor<1cm) is attained, this HIPEC (hyperthermic intraperitoneal chemotherapy) could be considered. For the primary advanced epithelial ovarian cancer, HIPEC will be performed at random. For the recurrent ovarian cancer, HIPEC will be performed after completion of cytoreductive procedures. Usually, HIPEC takes one and half hours after cytoreductive surgery. After cytoreductive surgery followed by HIPEC, adjuvant chemotherapy will be added. The cycle of chemotherapy will be determined according to the patients' clinical outcomes. The laboratory test results, image result, patient's medical history, and baseline quality of life will be checked after the operation, during chemotherapy, and after chemotherapy. Cytoreduction: an operation to remove ovarian cancer and its metastatic disease There will be an interim analysis when 50% of patients are enrolled. At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

Official Title
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Randomized Trial of Intraoperative Hyperthermic Intraperitoneal Chemotherapy Followed by Intravenous Chemotherapy in Patients With Ovarian Cancer

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Procedure: Hyperthermic Intraperitoneal Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease status Primary ovarian cancer, tubal cancer, and primary peritoneal cancer (Stage III or more) Residual tumor < 1cm after completion of cytoreductive surgery Age < 75 year 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 Adequate hepatic function Bilirubin ≤ 1.5 mg/dl and AST and ALT ≤ 80 IU/L Optimal cardiopulmonary function for surgery Voluntary participation after getting written informed consent. Exclusion Criteria: Unresectable extraperitoneal metastasis (brain, bone, lung parenchyme, and supraclavicular lymph node) Suboptimal debulking (residual tumor > 1cm) Previous History of other malignancies (except excision of skin cancer, thyroid cancer) Serious heart disease or renal failure Serious cardiopulmonary insufficiency Uncontrolled infection Uncontrolled intercurrent disease Psychogenic disorder Patients who are suitable candidates by legally Pregnant or breast-feeding patients Patients who are unsuitable candidates by doctor's decision MMMT Cancer tissue is not confirmed during surgery after neo-adjuvant chemotherapy

Ages Eligible for Study
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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
Interventional Model Description: HIPEC vs. no HIPEC after primary cytoreductive surgery or interval cytoreductive surgery
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIPEC<br>Intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Ovarian Cancer after primary cytoreductive surgery or interval cytoreductive surgery | Procedure: Hyperthermic Intraperitoneal Chemotherapy<br>* 41.5 oC injected into the perfusion cisplatin (75 mg/m2)during 90min<br>* Other names: Belmont Instrument Corporation;|
| No Intervention: No HIPEC<br>Primary cytoreductive surgery or interval cytoreductive surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | To assess progression free survival rate during 2 years after Intraoperative Hyperthermic Intraperitoneal Chemotherapy followed by Intravenous Chemotherapy in Patients with Ovarian Cancer. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, quality of life | Ovarian cancer patients after HIPEC are observed complication and 3-year survival rate. Ovarian cancer patients after HIPEC are analyzed quality of life. | 3 years |