phase 3 trial evaluating hyperthermic intraperitoneal chemotherapy in upfront treatment of stage iiic epithelial ovarian cancer

Conditions: Ovarian Neoplasms

Summary: 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.

Eligibility criteria:
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.

Keywords: hipec ovarian cancer cytoreductive surgery