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The most complete cytoreductive surgery possible (ideally macroscopically complete) followed by a closed-abdomen hyperthermic intraoperative peritoneal chemotherapy (HIPEC), using a closed circuit connected to the self-regulating Cavitherm machine (EEC certified). This perfusion apparatus records temperature, flow, and pressure for 90 minutes at real temperature (42-43°C).

The dialysate is made up of peritoneal dialysis fluid containing 0.7 mg/kg of MMC and increasing doses of irinotecan added to the dialysate the last 30 minutes of the HIPEC.

Potentiation of irinotecan using an intravenous FUFOL perfusion at least 1hour before HIPEC (1st dose level: 10 mg/m² of folinic acid, then 200 mg/m² of 5-FU; 2nd dose level: 20 mg/m² of folinic acid, then 400 mg/m² of 5-FU).

cytoreductive surgery and HIPEC

This is an open, non-randomized, phase I-II, pilot study, which evaluates the combination of optimum cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) with mitomycin C (MMC) and irinotecan. The latter drug will be administered in escalating doses to patients with gastric, colorectal, appendicular, or primary peritoneal carcinosis (PC).

Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

postoperative complications (class III and IV, Common Terminology Criteria V3; National Cancer Institute)

Plasma, peritoneal, and urinary values for MMC, irinotecan, SN-38, SN-38G, APC, and NPC.

Hospices Civils de Lyon

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Rare Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

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Ovarian Cancer

Ovarian Epithelial Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with CDDP+Paclitaxel

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.

Cytoreductive Surgery and HIPEC

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.)

CRS alone

Luca Ansaloni, MD

Marco Lotti, MD

Ingo B. Runnebaum, MD, MBA

Pierandrea Deiaco, MD

Fausto Catena, MD

Giovanni Scambia, MD

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).

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.

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

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.

percentage of patients in both arms completing the scheduled postoperative chemotherapy and time elapsed to start postoperative chemotherapy

Clinical Organization for Strategies & Solutions (CLIOSS), former Nerviano Medical Sciences (http://www.nervianoms.com/en/)

Onlus Cancro Primo Aiuto (http://www.cpaonlus.it/)

A.O. Ospedale Papa Giovanni XXIII

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan	NCT01226550	Peritoneal Carc...	cytoreductive s...	18 Years - 64 Years	Hospices Civils de Lyon
Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan	NCT01226550	Peritoneal Carc...	cytoreductive s...	18 Years - 64 Years	Hospices Civils de Lyon
Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer	NCT01628380	Ovarian Neoplas...	Cytoreductive S... CRS alone	18 Years - 70 Years	A.O. Ospedale Papa Giovanni XXIII
Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer	NCT01628380	Ovarian Neoplas...	Cytoreductive S... CRS alone	18 Years - 70 Years	A.O. Ospedale Papa Giovanni XXIII
Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer	NCT01628380	Ovarian Neoplas...	Cytoreductive S... CRS alone	18 Years - 70 Years	A.O. Ospedale Papa Giovanni XXIII

Spots Global Cancer Trial Database for cytoreductive surgery and hipec