Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer

Study Overview
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Brief Summary
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Aim of the Study is to compare two-years disease-free survival of Cytoreductive Surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC, CDDP+Paclitaxel) vs CRS alone in Stage IIIC unresectable epithelial tubal/ovarian cancer with partial or complete response after 3 cycles of 1st line chemotherapy (CBDCA +Paclitaxel).

Detailed Description
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Eligible: Female adult women (18 to 70 years old) patients, with epithelial ovarian/tubal (FIGO stage IIIC) with a Fagotti modified Laparoscopic Scoring System ≥ 4 who will show a complete or partial clinical response(RECIST 1.1) after 3 cycles of neoadjuvant chemotherapy (Carboplatin+Paclitaxel). Duration of recruitment: 2 years. Sample size has been calculated to reach a confidence level of 95% with a power of 80%, considering a 45% and 75% disease-free survival at 2 years in CRS and CRS+HIPEC group respectively. Sample size will be 47 patients for each group. After CRS, only patients with adequate cytoreduction (CC 0-1, residual tumor ≤ 2.5mm) will be randomized. Patients with suboptimal cytoreduction (CC 2-3, residual tumor > 2.5mm) are not suitable for randomization. The drug schedule elected in the current study is Cisplatin (CDDP) (100 mg/m2 of body surface area) + Paclitaxel (175mg/m2 of body surface area). Closed/open technique, as preferred. Duration: 90 minutes. Mean Intra-abdominal Temperature: 42°C. Primary Endpoint: 2-years disease-free survival. Secondary Endpoints: 1-year, 3- and 5-years disease-free survival; 1 month, 1-year, 3- and 5-years overall survival; toxicity induced by HIPEC using the NCI CTC criteria; one month and six months morbidity; duration of operation; return of bowel function; length of hospital stay; return to normal activity; six months and one year QOL, using the SF-36 v1.0; percentage of patients in both arms completing the scheduled postoperative chemotherapy; Subgroup analysis: PCI ≤ 15; pts. ≤ 40yrs. Main topics of this Study: Focused only on upfront treatment of primary disease. Select platinum-sensible patients (responders to platinum-based neoadjuvant chemotherapy). Take advantage of NACT to maximize chances for cytoreduction. Standardized strategy for CRS: radical surgery, associated to any surgical procedure needed to obtain a zero or ≤ 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.). Pelvic and peri-aortic lymphadenectomy is not chosen as standard procedure, but should warrant adequate staging. Compare only the effect of HIPEC.

Official Title
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Stage IIIC Unresectable Epithelial Ovarian/Tubal Cancer With Partial or Complete Response After 1st Line Neoadjuvant Chemotherapy (3 Cycles CBDCA+Paclitaxel): a Phase 3 Prospective Randomized Study Comparing Cytoreductive Surgery + Hyperthermic Intraperitoneal Chemotherapy (CDDP+Paclitaxel) + 3 Cycles CBDCA+Paclitaxel vs Cytoreductive Surgery Alone + 3 Cycles CBDCA+Paclitaxel.

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Procedure: Cytoreductive Surgery and HIPEC
* Procedure: CRS alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female adult women (18 to 70 years old) patients, with EOC (FIGO stage IIIc) with a Fagotti modified Laparoscopic Scoring System ≥ 4 who will show a complete clinical response (cCR) or partial clinical response (cPR) after 3 cycles (Carboplatin+Paclitaxel) of neoadjuvant chemotherapy; performance status (ECOG) 0, 1 or 2; signed informed consent. Exclusion Criteria: refusing to sign an informed consent; age > 70 years and age <18 years; BMI > 35; impossibility of an adequate follow-up; presence of other active neoplasms; active infection or other concurrent medical condition that could interfere in the ability of patients to receive the proposed treatment according to protocol; extraabdominal metastases (Stage IV) ; performance status (ECOG)>2; complete bowel obstruction; Abnormal bone marrow indices or renal and liver function; ASA IV or V.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CRS + HIPEC<br>Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with CDDP+Paclitaxel | Procedure: Cytoreductive Surgery and HIPEC<br>* CRS: radical surgery, associated to any surgical procedure needed to obtain a zero or ≤ 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.). HIPEC: Cisplatin (CDDP) (100 mg/m2 of body surface area) + Paclitaxel (175mg/m2 of body surface area). Closed/open technique, as preferred. Duration: 90 minutes. Mean Intra-abdominal Temperature: 42°C.<br>|
| Active Comparator: CRS alone<br>Cytoreductive Surgery alone | Procedure: CRS alone<br>* CRS: radical surgery, associated to any surgical procedure needed to obtain a zero or ≤ 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative morbidity and mortality |  | 1 and 6 months | 
| Time to Chemotherapy | percentage of patients in both arms completing the scheduled postoperative chemotherapy and time elapsed to start postoperative chemotherapy | 3 months | 
| Overall Survival |  | 1, 3 and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIPEC, Ovarian Cancer, Cytoreductive Surgery