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

A.O. Ospedale Papa Giovanni XXIII

Status and phase: Unknown; Phase 3

Conditions: Ovarian Neoplasms

Treatments: Procedure: CRS alone; Procedure: Cytoreductive Surgery and HIPEC

Study type: Interventional

Funder types: Other

Identifiers

NCT01628380

CHORINE 2012-002616-22

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 94 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups

CRS + HIPEC

Active Comparator group

Description:

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with CDDP+Paclitaxel

Treatment:

Procedure: Cytoreductive Surgery and HIPEC

CRS alone

Active Comparator group

Description:

Cytoreductive Surgery alone

Treatment:

Procedure: CRS alone